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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 73 records · Page 4Linked to original sources

High proliferative activity is associated with dysplasia in ulcerative colitis.

PURPOSE: Ulcerative colitis is associated with an increased risk of colorectal neoplasia. Markers of proliferation are reported to be valuable in the diagnosis of dysplasia in ulcerative colitis. However, it is not known whether dysplastic change or proliferative change occurs first. Whether abnormal proliferation is present in normal-seeming mucosa in ulcerative colitis was investigated. METHODS: Eighteen cancer or high-grade dysplasia specimens and 9 low-grade dysplasia specimens from 5 patients and 51 specimens from 31 patients without neoplasia were studied. Immunostaining with anti-Ki 67 antibody was used to evaluate proliferative activity. Labeling index (in the superficial one-half of crypt) was calculated. Crypts with labeling index more than 0.3 were determined to have abnormal proliferation. RESULTS: The mean +/- standard error of the mean labeling index in specimens negative for dysplasia (0.056+/-0.004) was significantly lower than that in low-grade dysplasia specimens (0.418+/-0.024) and that in high-grade dysplasia specimens (0.503+/-0.027; P < 0.0001). In specimens negative for dysplasia, only 4 (4 cases) of 339 (1.2 percent) crypts had abnormal proliferation, whereas the ratio of crypts with abnormal proliferation was 76 percent (54/71) in low-grade dysplasia and 92.1 percent (35/38) in high-grade dysplasia. The labeling index in background mucosa was 0.139+/-0.009, which was significantly higher than that in specimens negative for dysplasia (P < 0.001). In background mucosa 15.7 percent of crypts showed abnormal proliferation. A follow-up study revealed that two of four cases developed cancer or high-grade dysplasia one and seven years after proliferative abnormality was detected in nondysplastic specimens. CONCLUSION: Ki-67 immunostaining can be an aid in the diagnosis of dysplasia. High proliferating activity in background mucosa suggests that proliferating activity change precedes dysplasia detected with hematoxylin-and-eosin staining.

Biomarkers↗

Flat adenoma of the large bowel: re-evaluation with special reference to central depression.

PURPOSE: The aim of this study was to re-evaluate the clinicopathologic features of flat adenomas with special reference to the role of central depression found in flat adenomas. METHODS: Clinicopathologic features, such as grade of atypia by size, site, central depression, coexisting lesions, gender, and family history of cancer, were evaluated in 236 flat adenomas from 183 patients selected retrospectively and prospectively. RESULTS: Of the 236 flat adenomas, 175 had mild, 33 had moderate, and 28 had severe (i.e., intramucosal carcinoma) atypia. The frequency of severe atypia correlated positively with size. Severe atypia were significantly more frequent in females (21 percent in females and 10 percent in males; P < 0.05). Sixteen percent of flat adenomas in patients with coexisting cancer showed severe atypia, which was significantly more than those without coexisting cancer (P < 0.05). The frequency of multiple flat adenomas in patients with two or more family members with cancer was 53 percent, which was significantly higher than in patients with one or no family members with cancer (P < 0.05). Central depression was observed in 19 percent of flat adenomas. The rate of severe atypia (22 percent) of flat adenomas with central depression was significantly higher than that (9 percent) of flat adenoma without central depression (P < 0.05). Patients who had flat adenomas with central depression had a higher incidence of coexisting cancer and cancer in the family (P < 0.05 and P < 0.01). CONCLUSION: At colonoscopic examination consideration should be given for the increased potential to become malignant in flat adenomas, especially those with central depression and in patients with a history of malignancy or with a family history of malignancy.

Adenoma↗

Relation between thymidylate synthase expression and survival in colon carcinoma, and determination of appropriate application of 5-fluorouracil by immunohistochemical method.

BACKGROUND: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied. METHODS: Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup. RESULTS: Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439). CONCLUSIONS: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.

Antimetabolites, Antineoplastic↗

Colorectal carcinogenesis based on molecular biology of early colorectal cancer, with special reference to nonpolypoid (superficial) lesions.

The multistep genetic model of colorectal carcinogenesis is based on the concept of the adenoma-carcinoma sequence. The adenoma-carcinoma sequence theory has been generally accepted for polypoid early colorectal cancers (ECCs). On the other hand, an increasing number of nonpolypoid (superficial) ECC have been reported. Nonpolypoid (superficial) ECCs show distinct characteristics histologically and genetically, and some claim these lesions may develop by de novo type carcinogenesis. In fact, clinicopathologic studies have shown that most nonpolypoid (superficial) cancers have no adenomatous lesions in the surrounding area. Genetic analyses have also revealed that nonpolypoid (superficial) ECCs show a pattern of genetic alterations different from that of polypoid ECCs. The K-ras mutation rate is lower in nonpolypoid (superficial) ECCs than in polypoid ECCs, but there is no significant difference in the p53 mutation rate between two types of tumor. During the development of ECCs, the K-ras gene seems to determine the macroscopic configuration: whether polypoid or nonpolypoid (superficial). These results suggest that nonpolypoid (superficial) ECCs originate from a pathway different from the conventional genetic pathway that follows the adenoma-carcinoma sequence. However, this does not mean that this new pathway is following de novo type carcinogenesis, because there is a possibility that nonpolypoid (superficial) adenomas, or so-called flat adenomas, develop into nonpolypoid (superficial) ECCs following the adenoma-carcinoma sequence. At the present time, there is still not enough evidence to conclude whether nonpolypoid (superficial) ECC is derived from de novo carcinogenesis or the conventional adenoma-carcinoma sequence. Further analysis, especially concerning APC gene mutation in ECCs, is essential to elucidate the carcinogenesis of nonpolypoid (superficial) ECCs.

Adenoma↗

Endorectal ultrasonography and treatment of early stage rectal cancer.

The purpose of this study was to evaluate the accuracy of preoperative staging by endorectal ultrasonography (EUS) and its contribution to treatment of early stage rectal cancer (ESRC). The results of EUS for 154 consecutive patients with ESRC (pTis to pT2) were compared prospectively with histologic findings, assessed according to the TNM classification. Results of treatment selection and long-term outcomes were analyzed retrospectively. There were 35 patients histologically staged as pTis, 8 as pT1-slight (invasion confined to the superficial one-third of the submucosa), 37 as pT1-massive (invasion extending to the deeper submucosa), and 74 as pT2. The equipment used was an echoendoscope GF-UM2 or GF-UM3 (Olympus, Tokyo, Japan). Sensitivity/specificity/overall accuracy rates for detection of slight submucosal invasion, massive submucosal invasion, and muscularis propria invasion were 99%/74%/96%, 98%/88%/97%, and 97%/93%/96%, respectively. Incidences of lymph node metastasis in pTis, pTis to pT1-slight, pT1, pT1-massive, and pT2 cases were 0%, 0%, 18%, 22%, and 30%, respectively. Incidences of lymph node metastasis in ESRCs staged by EUS (u) as uTis, uT1-slight, uT1-massive, uT2, and uT3 by EUS were 0%, 0%, 26%, 36%, and 64%, respectively. Sensitivity, specificity, and overall accuracy rates for detection of positive nodes in overall ESRCs were 53%, 77%, and 72%, respectively. Of the 43 patients with pTis to pT1-slight tumors, 22 underwent endoscopic polypectomy or local excision, 20 radical surgery, and 1 radical surgery after endoscopic polypectomy due to vascular invasion. All these patients are alive and all but one (who refused radical surgery due to vascular invasion after local excision and developed liver and lung metastases) are disease-free. Of the 37 patients with pT1-massive tumors, 34 underwent radical surgery and 3 transcoccygeal segmental resection. All these patients are alive disease-free except for one who died of peritoneal carcinomatosis after radical surgery. All patients with pT2 tumors underwent radical surgery. The overall 5-year survival rates for pTis, pT1, and pT2 cases were 100%, 98%, and 97%, respectively. EUS is an accurate method for evaluating invasion depth in ESRC. Patients with uTis or uT1-slight tumors staged by EUS are at low risk of positive nodes and good candidates for endoscopic polypectomy or local excision. Those with uT1-massive or uT2 lesions should be treated with a radical operation because of the high incidence of positive nodes.

Adenocarcinoma↗

Analysis of Japanese occupational health services for small-scale enterprises, in comparison with the recommendations of the Joint WHO/ILO Task Group.

OBJECTIVES: To evaluate Japanese occupational health services (OHSs) for small-scale enterprises (SSEs). METHODS: The current Japanese OHSs for SSEs were compared with 15 recommendations of the Joint WHO/ILO Task Group. The status of OHSs was analyzed using the published papers collected by means of a computerized literature search. Thirty-five papers were used in the analysis, which was first conducted by the four authors separately, followed by discussion among the authors. Evaluation was conducted by classifying the status of Japanese OHSs for SSEs into three classes (A: good, B: average, C: poor) based on comparison with each recommendation. RESULTS: Six issues were evaluated as "A": establishment of a national policy for the provision of OHSs for SSEs, occupational health and safety inspection for SSEs, legislation to ensure services for SSEs and provision of financial incentives, adoption of occupational health programs using multiple channels, training in occupational health issues, and establishment of national data collection and registration systems. Nine issues were evaluated as "B": provision of OHSs for all SSEs as a part of the "national Health for ALL" strategy, intervention combining economic development and OHSs, extension of OHSs to vulnerable groups, coverage of migrant and seasonal workers by OHSs, the establishment of a national collaborative and coordinative body on OHSs, control of transfer of hazardous technology, encouragement of applied research, employers' commitment and worker participation, and integration of OHSs with primary health care. None of them was evaluated as "C". CONCLUSIONS: Japanese OHSs for SSEs were fairly well established in terms of compliance with the recommendations of the Joint WHO/ILO Task Group, although evaluation may be somewhat subjective and rather qualitative.

Facility Regulation and Control↗

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer.

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K-ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K-ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K-ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P< 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K-ras mutation and CEA level in pancreatic juice, as well as serum CA19-9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K-ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.

Adult↗

Predictive value of histology at the invasive margin in the prognosis of early invasive colorectal carcinoma.

To accurately select patients with malignant colorectal polyps who are at high risk of adverse outcome, we examined the predictive value of clinicopathological factors, with special attention paid to the histology at the invasive margin. We examined 75 submucosal carcinomas from 75 patients, initially resected by polypectomy, including endoscopic, trans-anal, trans-sacral, and trans-sphincteric local excision. The associations between clinicopathological features such as sex and age; tumor size, location, shape, depth of submucosal invasion, vascular invasion, histology at the central part, and histology at the invasive margin; and the presence or absence of a residual adenomatous component and adverse outcome were examined by univariate and multivariate logistic regression analyses. Lymph node metastases were found in 2 patients, local recurrence in 4, and distant metastases in 2. Univariate logistic regression analysis showed that unfavorable histology at the invasive margin was significantly associated with lymph node metastasis or local recurrence (P = 0.0373), whereas the association of lymphatic invasion and vascular (lymphatic or venous) invasion with lymph node metastasis or local recurrence had marginal significance (P = 0.0785; P = 0.0990). Multivariate logistic regression analysis, with unfavorable histology at the invasive margin and lymphatic invasion as independent variables, showed that unfavorable histology alone had significance (P = 0.0373) in predicting adverse outcome. Widely accepted criteria such as massive submucosal invasion, positive vascular invasion, and poorly differentiated histology, were less useful in predicting adverse outcome. These results suggest that unfavorable histology at the invasive margin is a useful risk factor for predicting lymph node metastasis or local recurrence in patients with malignant colorectal polyps.

Adult↗

Tacrolimus in corticosteroid-resistant ulcerative colitis.

We report a case of refractory ulcerative colitis treated with tacrolimus. The patient was a 73-year-old woman with a 45-year history of ulcerative colitis. An attack unresponsive to intravenous corticosteroid therapy occurred when she was age 73. Leukocytapheresis therapy was attempted, but was discontinued because of the patient's poor general condition. Cyclosporine A therapy brought about fair control of the disease. A liver injury that was suspected to be associated with this agent, however, occurred within 5 weeks of its initiation. At that time, the cyclosporine A was discontinued and azathioprine treatment was started. Within 6 weeks, signs of exacerbation of the ulcerative colitis became apparent. Tacrolimus administered at that time brought about remission of the disease, and the corticosteroid dose was then reduced. Tacrolimus, like cyclosporine A, appears to be effective for the treatment of attacks of ulcerative colitis.

Aged↗

Successful surgical treatment for spontaneous retroperitoneal hematoma in polycythemia vera: report of a case.

Bleeding is a common complication of such myeloproliferative disorders as polycythemia vera, and it usually occurs in either the skin or mucosa. We experienced a case of a massive retroperitoneal hematoma with no history of trauma in association with polycythemia vera. A 68-year-old man was referred to our hospital as a case of acute abdomen, and was diagnosed as having a retroperitoneal hematoma and polycythemia vera based on radiological and hematological examinations. Because the mass effect of the hematoma caused a progressive deterioration of his respiratory condition, surgical drainage was necessitated and successfully undertaken. Although conservative treatment is reportedly sufficient and uncontrollable intraoperative bleeding may occur, especially in cases of myeloproliferative disorders, our experience suggests that an operation may nevertheless be occasionally advisable for this rare condition.

Aged↗

Results of surgical treatment for vascular injuries.

The purpose of this study was to clarify the current etiology of and prognosis for iatrogenic vascular injuries. The study involved patients who underwent surgery for vascular injury. The patient record was retrospectively reviewed to collect information on the patient profile and type of vascular injury. The surgical techniques used were classified as simple or complex. The outcome was measured as morbidity and 30-day hospital mortality due to vascular injuries. The average age of the group with iatrogenic injury was significantly older than the group without. The number of males and females with iatrogenic injuries were almost equal, whereas males predominated in the group with noniatrogenic injuries. During the first half of the study period, more injuries were noniatrogenic; during the second half, most were iatrogenic. Most injuries due to angiographic procedures could be treated by a simple repair. Injuries due to operative procedures and noniatrogenic traumas had to be repaired by complex techniques. The overall morbidity rate was 3.8%, and the 30-day hospital mortality rate was 1.9%. The recently developed minimally invasive surgical techniques tend to increase the risk of vascular injuries whereas catheterization remains the most important cause of iatrogenic vascular injuries. However, as long as such injuries are treated promptly, the prognosis is good.

Adult↗

Psoas abscess complicating Crohn's disease: report of a case.

We describe herein the case of a psoas abscess complicating Crohn's disease, and present a review of the literature on this unusual disease entity. A 22-year-old Japanese man with a 5-year history of Crohn's ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient's symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient's condition greatly improved. The resected specimen showed Crohn's ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn's disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay.

Adult↗

Maternal program of apoptosis activated shortly after midblastula transition by overexpression of S-adenosylmethionine decarboxylase in Xenopus early embryos.

When we studied polyamine metabolism in Xenopus embryos, we cloned the cDNA for Xenopus S-adenosylmethionine decarboxylase (SAMDC), which converts SAM (S-adenosylmethionine), the methyl donor, into decarboxylated SAM (dcSAM), the aminopropyl donor, and microinjected its in vitro transcribed mRNA into Xenopus fertilized eggs. We found here that the mRNA injection induces a SAM deficient state in early embryos due to over-function of the overexpressed SAMDC, which in turn induces inhibition of protein synthesis. Such embryos developed quite normally until blastula stage, but stopped development at the early gastrula stage, due to induction of massive cell dissociation and cell autolysis, irrespective of the dosage and stage of the mRNA injection. We found that the dissociated cells were TUNEL-positive, contained fragmented nuclei with ladder-forming DNA, and furthermore, rescued completely by coinjection of Bcl-2 mRNA. Thus, overexpression of SAMDC in Xenopus embryos appeared to switch on apoptotic program, probably via inhibition of protein synthesis. Here, we briefly review our results together with those reported from other laboratories. After discussing the general importance of this newly discovered apoptotic program, we propose that the maternal program of apoptosis serves as a surveillance mechanism to eliminate metabolically severely-damaged cells and functions as a 'fail-safe' mechanism for normal development in Xenopus embryos.

Adenosylmethionine Decarboxylase↗

E-selectin can mediate the arrest type of adhesion of colon cancer cells under physiological shear flow.

The aim of this study was to determine whether colon cancer cells flowing in blood exhibit the same adhesion pattern to the vascular bed as leucocytes using a flow adhesion system. In shear flow conditions, five colon cancer cell lines showed less tethering to E-selectin substrates than polymorphonuclear cells (PMN). However, some of the Colo201 cells formed complete arrest on E-selectin in continuous shear flow which was never observed in PMN cells. Colo201 cells expressed both sialyl Le-x and sialyl Le-a at similar levels in flow cytometry. However, the staining pattern showed marked contrast under the fluorescein microscope. The cell membrane of Colo201 cells was uniformly stained with anti-sialyl Le-a MAb, whereas anti-sialyl Le-x MAb only stained in the patchy areas. Pretreatment of Colo201 cells with anti-sLe-a decreased tethering, while anti-sLe-x significantly inhibited the arrest formation. Our data suggest that E-selectin alone can mediate colon cancer cell lodgement and subsequent metastasis without the contribution of integrin molecules and that the different distribution of E-selectin ligands may affect the adhesion behaviour of colon cancer cells in flow conditions.

Cell Adhesion↗

Purification and characterization of organic solvent-stable lipase from organic solvent-tolerant Pseudomonas aeruginosa LST-03.

An organic solvent-stable lipase (LST-03 lipase) secreted into the culture broth of the organic solvent-tolerant Pseudomonas aeruginosa LST-03 was purified by ion-exchange and hydrophobic interaction chromatography in the presence of 2-propanol. The purified enzyme was homogeneous as determined by SDS-PAGE. The molecular mass of the lipase was estimated to be 27.1 kDa by SDS-PAGE and 36 kDa by gel filtration. The optimum pH and temperature were 6.0 and 37 degrees C. LST-03 lipase was stable at pH 5-8 and below 40 degrees C. Its hydrolytic activity was highest against tricaproin (C6), methyl octanoate (C8), and coconut oil respectively among the triacylglycerols, fatty acid methyl esters, and natural oils investigated. The enzyme cleaved not only the 1,3-positioned ester bonds, but also the 2-positioned ester bond of triolein. It exhibited high levels of activity in the presence of n-decane, n-octane, DMSO, and DMF as well as in the absence of an organic solvent. In addition, LST-03 lipase was stabler in the presence of n-decane, ethyleneglycol, DMSO, n-octane, n-heptane, isooctane, and cyclohexane than in the absence of an organic solvent.

Journal Article↗

Health risks among Japanese men with moderate body mass index.

BACKGROUND: Despite the westernized lifestyle, most Japanese are not prominently obese. As their obesity may be obscured, we want to further explore central fat distribution and health risks among this population. METHODS: 2668 men (body mass index (BMI) 20- < 26.4 kg/m2) were identified from 3343 men (BMI 14.0-37.7, median of waist-to-height ratio (W/Ht) 0.50) who underwent routine health examinations. They were divided into four groups: (1) BMI 20- < 24, W/Ht < 0.50; (2) BMI 20- < 24, W/Ht > or = 0.50; (3) BMI 24- < 26.4, W/Ht < 0.50; and (4) BMI 24- < 26.4, W/Ht > or = 0.50. The metabolic risks and physical activities were compared. RESULTS: W/Ht > or = 0.50 comprised 35% of the subjects of BMI 20- < 24, 91% of BMI 24- < 26.4, only 1% of BMI < 20 and up to 99% of BMI > or = 26.4. After adjusting for age and smoking and with group 1 as the reference group, odds ratios (ORs) were significantly higher in both groups 2 and 4 for the risk of hypertension (1.42, 1.98), hyperglycaemia (1.49, 1.78), hypertriglyceridaemia (1.95, 2.56), low HDL cholesterol (1.87, 2.20), hyperuricaemia (2.00, 2.51) and fatty liver (2.57, 5.64) and additionally in group 4 for hypercholesterolaemia (1.35). ORs in group 3 were only significantly higher for risk of hypertension (1.86) and fatty liver (1.89). Significantly lower frequencies of regular physical activity were noted in the higher W/Ht groups (0.75, 0.47, 1.10, 0.52 days per week, from groups 1-4, respectively). CONCLUSIONS: Measurement of waist circumference may be a preliminary method for the survey of people at higher risk of lifestyle-related disorders in Japanese men, especially among those with moderate BMI.

Abdomen↗

Near-infrared spectroscopy grades the severity of intermittent claudication in diabetics more accurately than ankle pressure measurement.

BACKGROUND: The aim of this study was to evaluate near-infrared spectroscopy (NIRS), combined with a treadmill-walking test, as a method of assessment of intermittent claudication (IC) in diabetic patients. METHODS: Some 208 symptomatic legs in 153 consecutive patients who complained of calf IC due to atherosclerotic disease were studied with NIRS and resting ankle : brachial pressure index (ABPI). RESULTS: There was good reproducibility of NIRS measurements. Three distinct types of IC were detected by NIRS. ABPI was significantly different between these three types in non-diabetic patients, but could not grade the severity of IC in diabetic patients. Recovery time (RT) of muscle oxygenation differentiated more accurately between severe and moderate claudication than ABPI in diabetics, although RT and ABPI had similar accuracy in non-diabetics. There was a significant correlation between RT and ABPI in non-diabetic patients and patients who had been diabetic for less than 10 years, while there was no correlation in patients who had had diabetes for over 10 years. CONCLUSION: Measurement of muscle oxygenation during exercise by NIRS graded the severity of IC in diabetic patients more accurately than resting ABPI. An abstract based on this paper was presented to the symposium of the 18th World Congress of the International Union of Angiology in Tokyo, Japan, September 1998

Adult↗