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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 127 records · Page 7Linked to original sources

Pulmonary blastoma: report of a case.

We herein describe a 27-year-old male presenting with a pulmonary blastoma. The patient was admitted to our hospital with the chief complaints of fever and left back pain. Chest roentgenograms showed a tumor measuring 10 cm in diameter in a lower lobe of the left lung. Computed tomography and magnetic resonance imaging revealed a well demarcated and heterogeneously enhanced tumor. Although a histological diagnosis could not be obtained by a transbronchial biopsy, image analyses led us to suspect it to be malignant. The patient underwent a left lower lobectomy with lymph node dissection. A histopathological examination revealed the tumor to be a biphasic type of pulmonary blastoma. Because of the rapid progress of the tumor and the difficulty in making a preoperative diagnosis in such cases, an immediate surgical resection is therefore recommended in cases with even the slightest suspicion of malignancy.

Adult↗

Organ-specific pancreatic tumor growth properties and tumor immunity.

We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection. Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from mice that rejected PancO2-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.

Amino Acid Sequence↗

Tachycardia as a potential risk indicator for coronary arterial lesions in Kawasaki disease.

UNLABELLED: Tachycardia is frequently observed in the acute phase of Kawasaki Disease (KD) patients. However, little is known about the association between the tachycardia in the acute phase of KD and the development of coronary arterial lesions (CAL). We examined the association between the mean 24 h heart rate in the acute phase of KD observed using 24 h ambulatory ECG monitoring (24 h-ECG) and the occurrence of CAL in patients. In a study conducted between 1994 and 1997, 26 patients with KD underwent 24 h-ECG within the febrile period and before the 9th day of illness. We compared the mean 24 h heart rate based on 24 h-ECG between patients with and those without CAL. Of 26 patients, 7 had CAL. The groups with and without CAL had similar baseline characteristics. The mean 24 h heart rate in the group with CAL was significantly higher than that in the group without CAL (144 +/- 14 vs. 124 +/- 22, P = 0.033). On multiple regression analysis, the mean 24 h heart rate was significantly correlated with the development of CAL (P = 0.019). CONCLUSION: Marked tachycardia detected by 24 h-ambulatory ECG monitoring in the acute phase of Kawasaki disease might provide important information on the development of coronary arterial lesions.

Acute Disease↗

Colorectal carcinoma: recent advances in its biology and treatment.

Recent advances in the molecular biology and treatment of rectal carcinoma were reviewed mainly on the basis of our own experience. Remarkable improvement in molecular biology has been achieved in the colorectal diseases, and the new knowledge derived from molecular genetics is now being used in the clinical field. The deeper understanding of colorectal carcinogenesis and wider clinical use of molecular diagnosis is one of the examples, and further advances are expected in the next century. Surgical advances are noted particularly in the field of rectal surgery. Various modalities make it possible to assess the clinical stage more precisely, which leads to careful application of the fine surgical procedures used to maintain urinary and sexual functions with low rates of local recurrence and prolonged survival. This decision making should be conducted and can be accomplished by experienced colorectal surgeons with the team members supporting them. The earlier the detection of disease, the easier the operation, with a lower risk of recurrence and longer survival; therefore, early detection of colorectal cancer by means of occult blood test is essential for this purpose. Establishment of the proper training system for appropriate colorectal surgery is also mandatory for this most common gastrointestinal cancer in the Western world, and this is also the case for Japan. The Japan Society for Cancer of the Colon and Rectum is expected to play an important role in this respect.

Colorectal Neoplasms↗

Rapid growth of residual colonic tumor after incomplete mucosal resection.

We report an 89-year-old man with colon cancer that developed rapidly after an incomplete endoscopic mucosal resection (EMR), and discuss the adverse effect of this maneuver on the tumor biology. A sessile polyp, 15 mm in size, was detected at the hepatic flexure. EMR was performed immediately. Histological examination showed well differentiated adenocarcinoma with an adenomatous component invading the submucosal layer. There was vascular invasion (positive on elastica van Gieson staining) and the surgical margin was positive for cancer. A right hemicolectomy was performed. The surgical specimen showed the residual tumor, 22 mm in diameter. The relevant histopathological findings of the surgical specimen were: well differentiated adenocarcinoma, with partly mucinous carcinoma and a tubular adenomatous component, depth muscularis propria (mp), lymph node (LN) (0/9). Most of the submucosally invasive cancer was resected by the initial EMR, but the small residual tumor showed rapid growth within only 3 months after the EMR. It was assumed that the residual tumor cells had acquired more malignant characteristics after EMR. In regard to EMR we propose that: (1) except for patients who are at high risk for a major operation, EMR should be avoided for carcinoma with massive submucosal invasion, (2) colonic resection should be performed immediately when histology shows a positive surgical margin for carcinoma, and (3) patients operated after an incomplete EMR should be watched very carefully for the detection of recurrence.

Adenocarcinoma↗

Functional expression of beta1 and beta2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer.

Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta1 and beta2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated alpha chains, the expressions of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha4 (CD49d) and alpha6 (CD49f) were markedly downregulated in TIL. Both alphaL (CD11a) and beta2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.

Aged↗

Severe complications of ulcerative colitis after high-dose prednisolone and azathioprine treatment.

We report a rare case of ulcerative colitis (UC) associated with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in multiple organs, and with compressive fracture from osteoporosis after the administration of high-dose prednisolone and azathioprine. A 25-year-old man had been treated with high-dose prednisolone for UC. He suddenly experienced severe lumbago, which prevented him from walking. Plain X-ray demonstrated compressive fractures of the thoracic and the lumbar vertebrae, which were thought to be due to osteoporosis as a side effect of the high-dose prednisolone. At this admission, in another hospital, he also had a bloody discharge from the rectum, and azathioprine was started; however, the patient's condition still did not show any improvement. The total doses of azathioprine and prednisolone he had received were 3150 mg and more than 15,000 mg, respectively. Considering the presence of the serious complications, surgical intervention was the treatment selected. Culture study revealed MRSA in the feces and nasal cavity, and P. aeruginosa in the feces and urine. Vancomycin hydrochloride and gentamicin were administered, and were effective, with a subsequent negative culture study. Subtotal colectomy with mucus fistula was performed. After the operation, culture studies remained negative. Major steroid side effects such as bone fracture and osteoporosis should be considered as an indication for surgery in UC patients. MRSA and P. aeruginosa are a menace, especially for UC immunosuppressed patients on steroid or immunosuppressive therapy. When these bacteria are detected, there should be prompt and adequate antimicrobial therapy against the organisms and the immunosuppressive therapy should be immediately discontinued. We conclude that surgical therapy should be considered in the earlier stage for patients with intractable UC, rather than continuing long-term administration of steroid or azathioprine, which may lead to serious complications.

Adult↗

Influence of popliteal vein thrombosis on subsequent ambulatory venous function measured by near-infrared spectroscopy.

BACKGROUND: To determine the influence of the site affected by thrombi on the subsequent venous physiology, we examined patients with postthrombotic syndrome (PTS) with respect to ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Fifty-one limbs of 45 patients, for whom more than 1 year had passed since an acute episode of deep vein thrombosis, were studied. Seventeen limbs were asymptomatic, 27 had mild symptoms (edema only), and 7 showed severe symptoms (skin changes). The mean duration of PTS was 8.2 years. All of the patients underwent a treadmill walking test with simultaneous NIRS. Deoxygenated hemoglobin was continuously measured during exercise. The ambulatory venous retention index (AVRI) obtained from the serial deoxygenated hemoglobin changes was calculated in each patient. The location of thrombi at the onset of deep vein thrombosis was identified by venography. RESULTS: The calculated AVRI was apparently related to the clinical symptoms of PTS. The limbs initially involved with popliteal vein thrombosis showed significantly higher AVRI values than those without popliteal vein thrombosis. CONCLUSIONS: The clinical severity of PTS is correlated well with the degree of venous retention during exercise. Initial involvement of the popliteal vein is an important factor determining subsequent venous hemodynamics in patients with PTS.

Adolescent↗

Gasless laparoscopically assisted colonic surgery.

BACKGROUND: Laparoscopic technique has been applied to a variety of colonic and rectal operations, generally using carbon dioxide insufflation (CDI). However, CDI is inevitably associated with cardiopulmonary loading and can cause complications. The objective of this study was to determine the feasibility of gasless laparoscopic colonic surgery. METHODS: The abdominal wall was lifted up using an originally designed retractor. A small incision, 3 to 5 cm in length, was made at the start of the operation. The surgeon operated through this incision using both conventional and laparoscopic instruments. RESULTS: Operations were undertaken in 67 patients. In 6 patients (9%), conversion to open surgery was necessitated. In the remaining 61 patients, operations were completed with gasless laparoscopically assisted technique. Four reoperations (7%) were performed because of postoperative bleeding, anastomotic rotation, anastomotic stricture, and transmesenteric hernia. Fifty-three patients with colonic cancer were operated on with potentially curative intent. Of these, 1 (2%) developed hepatic recurrence during the mean follow-up period of 23.8 months. There was no port site recurrence. CONCLUSIONS: Gasless laparoscopic colonic surgery is technically feasible. CDI is not necessary to perform minimal access surgery.

Carbon Dioxide↗

Growth hormone/insulin-like growth factor 1 axis alterations contribute to disturbed protein metabolism in cirrhosis patients after hepatectomy.

BACKGROUND/AIM: Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in cirrhosis to postoperative nitrogen metabolism are not known. METHODS: Plasma GH, IGF-1 and IGF binding protein 3 (IGF-BP3) levels were measured sequentially in patients undergoing hepatectomy with or without cirrhosis. Postoperative nitrogen excretion and whole-body protein turnover rate were also determined. RESULTS: Preoperative plasma IGF-1 level showed a negative correlation with indocyanine green retention rate. Cirrhosis patients undergoing hepatectomy had low IGF-1 and IGF-BP3 levels, despite extremely high GH levels in the perioperative period. Perioperative IGF-1 levels were lower in patients with postoperative complications than in those without complications. Postoperative nitrogen excretion was higher and whole-body protein turnover rate was lower in patients with cirrhosis than in those without cirrhosis. The post-operative IGF-1 level showed a positive correlation with whole-body protein turnover rate. CONCLUSIONS: Postoperative hepatic IGF-1 production may be severely disturbed in patients with cirrhosis, and the impaired IGF-1 production contributes to the suppressed postoperative protein metabolism in cirrhosis. It may be appropriate to increase plasma IGF-1 level in patients with cirrhosis to enhance postoperative protein metabolism and improve the postoperative outcome.

Aged↗

Prophylactic treatment with growth hormone and insulin-like growth factor I improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis.

The purpose of this investigation was to evaluate the effects of GH and IGF-I administration in a murine model of burn-induced gut-derived sepsis. BALB/C mice were treated with 4.8 mg/kg/day of GH, 24 mg/kg/day of IGF-I or saline for 4 days. They were then administered 10(10) E. coli by gavage and subjected to 20% full thickness flame burn. All mice received allogeneic blood transfusion 5 days before burn injury to induce mild immunosuppression. Seventy-three mice were observed for survival and 51 mice were sacrificed at 4 and 20 h postburn. Blood, mesenteric lymph nodes (MLN), spleen and liver were harvested aseptically, and viable bacterial counts in the organs were determined. The small intestine was harvested for the evaluation of villus height and mitoses in the crypts. GH and IGF-I groups showed a significantly better survival than the control group. GH and IGF-I groups had significantly greater villus height and mitoses/crypt than the control group. Translocation of bacteria was not significantly different among groups, however, the relation between the numbers of viable bacteria in MLN and blood suggests that both GH and IGF-I reduced systemic spread of translocated bacteria. It is concluded that GH and IGF-I had positive effects on outcome in this model of burn-induced gut-derived sepsis. It appears that GH and IGF-I may have immune-enhancing effects and that administration of these agents may be useful for burn injury.

Animals↗

Enteral administration of glutamine in purulent peritonitis.

The intestinal hypomotility associated with purulent peritonitis is generally regarded as a contraindication to enteral nutrition. However, enteral nutrition may be feasible in suppurative peritonitis if administered with great caution, i.e., assuring the appropriate amount, delivery speed, and osmolality of the enteral formulation. Glutamine (Gln) increases muscle protein synthesis and decreases muscle protein degradation in sepsis, regardless of the route of administration. Therefore, administering small amounts of supplemental Gln via the enteral route to peritonitis patients may be beneficial. Two purulent peritonitis patients received L-Gln through a jejunostomy tube. The average amount of supplemental Gln was 16 g/d. Systemic inflammatory responses, i.e., high temperature and a high serum C-reactive protein level, persisted throughout the treatment period. Femoral arterial and venous blood samples were drawn simultaneously for determination of amino acid levels before and after 7 d of Gln supplementation. Enterally administered Gln was well-tolerated by both patients. There was an increase in plasma Gln levels after Gln supplementation. Moreover, the release of Gln, alanine, and phenylalanine from the lower extremities was lower after as compared to before Gln supplementation. Enteral administration of Gln may be feasible even in purulent peritonitis.

Amino Acids↗

Crystallographic and functional studies of very short patch repair endonuclease.

Vsr endonuclease plays a crucial role in the repair of TG mismatched base pairs, which are generated by the spontaneous degradation of methylated cytidines; Vsr recognizes the mismatched base pair and cleaves the phosphate backbone 5' to the thymidine. We have determined the crystal structure of a truncated form of this endonuclease at 1.8 A resolution. The protein contains one structural zinc-binding module. Unexpectedly, its overall topology resembles members of the type II restriction endonuclease family. Subsequent mutational and biochemical analyses showed that certain elements in the catalytic site are also conserved. However, the identification of a critical histidine and evidence of an active site metal-binding coordination that is novel to endonucleases indicate a distinct catalytic mechanism.

Alanine↗

Effect of 5-fluorouracil on gastrointestinal carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

This study was undertaken to determine the effect of 5-fluorouracil on gastrointestinal carcinogenesis. Sixty rats were divided into three groups of 20 rats each. All rats were exposed to N-methyl-N'-nitro-N-nitrosoguanidine for the first 20 weeks. Group 1 rats received intraperitoneal injections of 5-fluorouracil for the first 20 weeks and were then observed for the second 20 weeks. Group 2 rats also received 5-fluorouracil injections, but for the second 20 weeks. Group 3 rats received no 5-fluorouracil treatment. Four of 20 rats in group 1 developed an invasive adenocarcinoma. In group 3, invasive squamous cell carcinoma and adenocarcinoma developed in one rat each. None of the group 2 rats had malignant lesions. These results suggested that 5-fluorouracil is not effective in suppressing the initial stage of gastrointestinal carcinogenesis with a coexisting carcinogen. Rather, the therapeutic effect is exerted in later stages of tumor progression.

Adenocarcinoma↗

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow.

Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous presence of shear flow. The tethering of Colo201 was partially inhibited by monoclonal antibodies (mAbs) to alpha6 integrin and a combination of mAbs to beta1 and beta4 integrins, but not by mAb to 67KD laminin receptor. Some Colo201 cells still tethered at 4 degrees C. This suggests that alpha6beta1 and alpha6beta4 integrins participate in Colo201 tethering on LM, although other non-integrin molecules play roles. In contrast, the spread of Colo201 was effectively inhibited by the mAbs to integrin alpha2, alpha6 and beta1 chains. The effect of anti-alpha2 plus anti-alpha6 mAbs was almost equal to anti-beta1, suggesting that Colo201 cells mainly use alpha2beta1 and alpha6beta1 integrins for spreading on LM. When the cells were perfused on subconfluent endothelial cells (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM exposed at intercellular gap area. Immunohistochemistry revealed that LM abundantly existed in the cytosol of human portal and hepatic vein endothelial cells. These data suggest that LM can mediate from tethering to spreading of colon cancer cells under the blood flow and plays an essential role in haematogeneous metastasis.

Antibodies, Monoclonal↗

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522.

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer.

Animals↗