IL-10: a tacrolimus-specific cytotoxic mediator in ongoing allograft rejection.
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Administration, Oral↗
Biomedical subjects
T Fujimura
Publications and source records attributed to T Fujimura.
Transgenic pigs with human N-acetylglucosaminyltransferase III.
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Animals↗
Production and characterization of a novel tissue-type plasminogen activator derivative in Escherichia coli.
We have created a novel thrombolytic agent by the combination of mutation with partial deletion of tissue-type plasminogen activator (t-PA). We constructed Escherichia coli expression vectors for (i) native t-PA (nt-PA) and its derivatives; (ii) K1K2P, consisting of kringle 1 (K1), kringle 2 (K2), and protease (P) domains; (iii) K2P, consisting of K2 and P domains; (iv) D-nt-PA; (v) D-K1K2P; and (vi) D-K2P. The latter three are point mutants of nt-PA, K1K2P, and K2P, respectively, in which Arg275 (number corresponds to that of nt-PA) has been mutated to Asp. The production of nt-PA and its derivatives was remarkably improved by (i) removal of the 3' noncoding region of nt-PA cDNA from expression vectors and (ii) expression in mutant E. coli derived from E. coli HB101, which is insensitive to heat-shock inductions. The proteins produced were precipitated as insoluble aggregates in the cells and were renatured to active forms by extraction with 8 M urea followed by dialysis against a redox buffer containing GSH and GSSG. The renaturation yield depended on the pH of the buffer and the number of disulfide bonds of the proteins (nt-PA << K1K2P < K2P). The mutation of Arg275 (the plasmin cleavage site) caused an increase in the catalytic enhancement by fibrin and a decrease of the interaction with plasminogen activator inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Partial left ventriculectomy for patients with ischemic cardiomyopathy.
BACKGROUND: Partial left ventriculectomy (PLV) has been performed in patients with dilated cardiomyopathy (DCM), but improved myocardial energetics may make PLV useful also for ischemic cardiomyopathy (ICM) unamenable to conventional treatment. METHODS: Of 262 patients undergoing PLV, 94 patients with ICM as the underlying pathology were analyzed and compared with 168 patients with DCM. RESULTS: ICM patients were older (57.3 years vs 50.9 years, p = 0.0001) and heavier (69.7 kg vs 65.9 kg, p = 0.039) than those with DCM, but ventricular end-diastolic and end-systolic dimensions were similar with comparably depressed fractional shortening (16% vs 15%, p = 0.294) and equally severe functional limitation [New York Heart Association (NYHA) Class 3.7 vs 3.6, p = 0.734]. A majority of patients in both groups underwent lateral PLV (76% vs 74%, p = 0.883) with myocardium excised between papillary muscles and simultaneous mitral valvuloplasty (41% vs 74%, p < 0.0001). Because ICM patients required coronary artery bypass grafting (CABG) more frequently (79% vs 0.6%, p < 0.0001), operation was more extensive in terms of bypass time (74 minutes vs 47 minutes, p < 0.0001), percentage requiring cardiac arrest (43% vs 19%, p < 0.0001), and arrest duration (34 minutes vs 28 minutes, p = 0.280), but all had similar resection and postoperative ventricular dimensions. Nonetheless, ICM patients required shorter intensive care unit (ICU) time (4.4 days vs 5.9 days, p = 0.048) and similar postoperative hospital stays, resulting in similar hospital survival rates (69% vs 71%, p = 0.778) and functional capacity in long-term follow-up. CONCLUSIONS: Results suggest that PLV can be performed in patients with ICM with comparable risks and benefits as in DCM. Relative efficacy of CABG and mitral repair as compared to volume reduction remains to be studied.
Adult↗
Association of a deletion polymorphism of the angiotensin-converting enzyme gene with left-ventricular hypertrophy in Japanese women with essential hypertension; multicenter study of 1,919 subjects.
The relationship of an insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to left-ventricular hypertrophy in individuals with essential hypertension (EH) was investigated in a large population of Japanese men and women. The ACE genotype of 762 subjects with EH (425 men and 337 women) and 1,157 healthy controls (604 men and 553 women) was determined by polymerase chain reaction analysis. The distribution of ACE genotypes did not differ significantly between patients with EH and control in both men and women. For women with EH, the DD genotype was positively associated with the thickness of the interventricular septum and inversely associated with the left ventricular end-diastolic dimension, both determined by echocardiography. In contrast, the DD genotype was not associated with any echocardiographic parameter in men with EH. These results indicate that the DD genotype is a risk factor for left-ventricular hypertrophy in Japanese women with EH, but not for Japanese men.
Adult↗
Association of immunohistochemical detection of urokinase-type plasminogen activator with metastasis and prognosis in colorectal cancer.
We evaluated urokinase-type plasminogen activator (uPA) expression with immunohistochemistry in 90 cases of colorectal cancer and compared it with the clinicopathological findings. Patients who had cancer cells which were stained intensively relative to the background were recognized as uPA-positive patients. The uPA-positive rate was 36.7% (33/90) in total cases. There was a significant correlation was also seen between uPA expression and liver metastasis. Prognosis was poorer in the uPA-positive patients than in the uPA-negative patients. Therefore, uPA may be a good predictor of metastasis and prognosis.
Adult↗
Correlation between electroencephalogram, hepatic encephalopathy grade, and biochemical indices in beagles with portacaval anastomosis.
The EEG, grades of hepatic encephalopathy, and biochemical indices of 16 beagles with portacaval anastomosis were recorded throughout their lives and correlations between these parameters were investigated. The degree of deterioration of some biochemical indices, such as the ammonia concentration, glutamate oxaloacetate transaminase and alkaline phosphatase activities in the plasma, and percentage loss of body weight showed a progressive increase parallel to the severity of the hepatic encephalopathy (HE) grade (grading scale O-IV), but other biochemical indices such as the concentrations of aromatic or branched-chain amino acids, the molar ratio of branched-chain to aromatic amino acids, or the total protein concentration in the plasma did not show such relationship. The SW ratio, an index of the incidence of slow-waves in the EEG, was calculated from frequency distribution histograms which were obtained by frequency analyses of EEG recordings. A slight but significant correlation was found between the SW ratio and the plasma ammonia concentration. In addition, the SW ratio consistently increased with increase in the HE grade, although the SW ratio in HE grade IV was below the normal range for beagles. These results show that only the ammonia concentration in the plasma correlates with deterioration of the HE grade and of the SW ratio, suggesting that changes in ammonia concentration in the plasma should be of diagnostic value in assessing changes in mental state and the EEG in patients with liver cirrhosis. The importance of ammonia in pathogenesis of HE is stressed.
Alanine Transaminase↗
Normalization of abnormal electroencephalograms in beagles with portacaval anastomosis by infusion of solutions rich in branched-chain amino acids.
The effects of intravenous infusions of amino acid solutions on the electroencephalograms (EEG) and biochemical indices of 12 beagle dogs with a portacaval anastomosis (PCA) were studied in unanesthetized and unrestrained conditions. EEGs were recorded everyday from 2 days after the operation. When the EEGs showed predominant delta and theta frequency bands (slow-wave), solutions of amino acids were infused intravenously at 5 ml/kg/hr for an hour. Blood was withdrawn immediately before and after the infusion to determine plasma amino acids and ammonia. Infusion of amino acid solutions enriched in branched-chain amino acids (BCAA) with restricted aromatic amino acids (AAA) normalized the predominantly slow-wave EEGs. These solutions reduced the increased plasma AAA and ammonia concentrations and increased the lowered plasma BCAA concentrations. The abnormal EEGs were not improved by infusion with a balanced and AAA-enriched amino acid solution for nutritional support of surgical patients and became worse on infusion of AAA solution. Significant correlations were found between percent changes in the incidence of slow-waves and plasma AAA concentrations. These results suggest that infusion of solution with low AAA and high BCAA concentrations may be suitable for treatment of cirrhotic patients with abnormal EEG or with hepatic encephalopathy.
Amino Acids↗
Immobilization of yeast cells by radiation-induced polymerization.
Radiation-induced polymerization method was applied to the immobolization of yeast cells. The effects of irradiation, cooling and monomer, which are necessary for polymerization, were recovered completely bu subsequent aerobic incubation of yeast cells. The ethanol productive in immobilized yeast cells increased with the increase of aerobic incubation period. The growth of yeast cells in immobilized yeast cell was indicated. The maximum ethanol productivity in immobilized yeast cell system was around three times as much as that in free yeast cell system.
Dose-Response Relationship, Radiation↗
Evaluation of p53, Ki-67 and DNA ploidy in both primary rectal carcinomas and locally recurrent tumors.
The object of this study was to evaluate cellular markers which included tumor cell p53 expression, cell proliferation antigens and DNA ploidy in both primary and locally recurrent rectal cancer. The study included 16 locally recurrent rectal cancer and 24 non-recurrent primary rectal cancer. Levels of p53 and Ki-67 expression were quantified and the DNA ploidy analyzed. In the locally recurrent group, labelling index of p53 was significantly higher in the short disease-free interval (DFI) (<2 years) group than the long DFI (> or = 2 years) group (p<0.05). It was immunohistochemically proved that DNA aneuploidy was reflected by accumulation of mutated p53 in both primary rectal cancer and locally recurrent tumors. The early local recurrence after curative operation for rectal cancer was associated with the number of p53 positive cells.
Adult↗
Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis.
Matrix metalloproteinase (MMP) expression is associated with advanced-stage cancer and contributes to tumor progression, invasion, and metastasis. Membrane type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at the C terminus and activates pro-MMP-2, which is mainly produced from interstitial fibroblasts. Its expression on the membrane of invasive tumor cells results in the pericellular space degradation at cell-matrix contact sites and renders cancer cells more invasive at the migration front. To elucidate the relationship between MT-MMP expression and metastasis and prognosis in gastric cancer patients, MT-MMP expression was analyzed immunohistochemically in 127 primary tumors and results were correlated with several prognostic parameters and patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with macroscopically invasive type, nodal involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001). Multivariate analysis showed MT-MMP overexpression as an independent prognostic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis of gastric cancer patients.
Adult↗
Subtotal peritonectomy with chemohyperthermic peritoneal perfusion for peritonitis carcinomatosa in gastrointestinal cancer.
Treatment for peritonitis carcinomatosa in gastrointestinal cancer remains to be established though it is one of the commonest causes of cancer death. Subtotal peritonectomy (SP) with chemohyperthermic peritoneal perfusion (CHPP) was developed for the new therapeutic strategy for peritoneal dissemination in gastrointestinal cancer in our department. SP includes resection of stomach, colon, small bowel, spleen, gall bladder, and parietal peritoneum. CHPP was carried out by heated saline containing 25 mg/l cisplatin, 10 mg/l mitomycin C, and 20 mg/l etoposide. Intraperitoneal temperature was maintained at 42 degrees C for 60 min. Fifteen gastric cancer and three colon cancer patients with severe peritoneal dissemination underwent these procedures. The averages of operating time, intraoperative bleeding volume, and total perioperative transfused blood volume were 9 h, 4400 ml, and 5600 ml, respectively. The patients estimated as complete resection and residual disease by histopathological study numbered 11 and 7. There was no treatment-related deaths though bleeding occurred in 5 patients; perforation in 2 patients; and abscesses in 2 patients. The 1-year survival rate (1ysr) and the 2-year survival rate (2-ysr) of all the patients were 57% and 21%, respectively. The 1-ysr and the 2-ysr of the patients who underwent complete resection were 67% and 40% significantly greater than the 43% and 0% of the patients who had residual tumors (p=0.02). The combination therapy of SP and CHPP is feasible in spite of its morbidity and has great possibilities in complete resection of peritoneal dissemination and prolongation of patient's survival.
Adult↗
A new surgical approach (peritonectomy) for the treatment of peritoneal dissemination.
BACKGROUND/AIMS: Despite the improvements of chemotherapy and surgical techniques, treatment results of peritoneal dissemination still remain pessimistic. METHODOLOGY: During a 10-year period, 106 patients with peritoneal dissemination from gastric cancer were treated with chemo-hyperthermic peritoneal perfusion (CHPP), peritonectomy + CHPP, systemic PMUE therapy, and surgery alone in 51, 15, 13, and 27 patients, respectively. In peritonectomy, disseminated nodules were resected as much as possible in combination with the combined resection of the abdominal organs and parietal peritoneum covering diaphragm, pelvis and abdominal wall. After resection, the abdominal cavity was treated with heated saline at 42-43 degrees, containing cisplatinum (CDDP), Mitomycin C (MMC), and etoposide for 1 hour. PMUE therapy was administered with one course of i.v. infusion of 75 mg/m2 of CDDP and 30 mg/body of MMC on the 1st day, followed by etoposide 50 mg/body on the 3rd, 4th, and 5th day, and with oral intake of 400 mg/body of UFT every day from the 1st day. RESULTS: No post-operative or chemotherapeutic deaths were observed. Systemic PMUE therapy showed no survival improvement, and survival of the peritonectomy + CHPP group was the best, following CHPP, systemic PMUE and surgery alone. CONCLUSIONS: Peritonectomy and CHPP may be the best choice for the treatment of peritoneal dissemination.
Adult↗
Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies.
A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.
Abdominal Neoplasms↗
Postoperative results of left upper abdominal evisceration for advanced gastric cancer.
BACKGROUND/AIMS: In spite of the improvement of surgical techniques, the prognosis of patients with advanced gastric cancer still remains poor. With the aim of achieving en bloc resection of primary tumor, peritoneal dissemination on the greater omentum and lymph node metastasis, left upper abdominal evisceration (LUAE) was performed for 75 patients. In this report, we investigated the prognostic difference between the LUAE group and standard gastrectomy (total gastrectomy + pancreatosplenectomy). METHODOLOGY: In the LUAE group, total gastrectomy was performed with the en bloc resection of the transverse colon, pancreas body and tail, spleen and left adrenal gland. In addition, omental bursa, covering retroperitoneum and pancreas body and tail was resected in combination with greater omentum, transverse mesocolon, and lesser omentum. RESULTS: There were 3 (4.1%) postoperative death in the LUAE group, and 2 (1.7%) in the control group. However, there was no statistical difference in the incidence of postoperative complications between these 2 groups. The overall 5-year survival rates of the LUAE and control groups were 33% and 39%, respectively. There was no statistical survival difference between these 2 groups. Survival difference between the LUAE and control group was not found in terms of tumor location, wall invasion, lymph node status, peritoneal dissemination, and macroscopic type. CONCLUSIONS: From these results, LUAE cannot improve the survival of patients with advanced gastric cancer. Consequently, LUAE should be indicated for T4 tumors, which directly invade into the transverse colon.
Adrenalectomy↗
Diurnal variation affects age-related profile in skin thickness.
We have previously demonstrated that over the course of each day there are changes in skin thickness that can be measured by B-mode ultrasonography. This suggests that there is a shift in dermal fluid from the face toward the legs by gravity, resulting in a diurnal variation in skin thickness. Therefore, age-dependent profiles in skin thickness were evaluated by B-mode ultrasonography in the morning or in the afternoon for 130 normal Japanese females aged 18-83 years. Three areas of the face (the forehead, the corners of the eye, and the cheeks) were measured as distinctively sun-exposed areas while the flexion side of the forearm was measured as a weakly sun-exposed area. A weak correlation between skin thickness and age was found in all areas measured (positive for the forehead, the corners of the eye, and the cheeks; negative for forearms) in the morning but not in the afternoon, when only a weak positive correlation was observed in the cheek. These results indicate that when measuring skin thickness, an appropriate time for taking measurements should be selected with consideration of the movements of dermal fluid over the course of each day.
Adolescent↗
Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.
BACKGROUND/AIMS: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer. METHODOLOGY: One-hundred and thirty-nine patients with T2-4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy. These patients were randomly allocated into the following three groups. Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion, and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion. The third group was surgery alone group. In the CHPP and CNPP groups, peritoneal cavity was perfused with 6-8 liters of heated saline at, respectively, 42-43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine. RESULTS: Major operative complication occurred in 19% (9/48), 14% (6/44) and 19% (9/47) of the CHPP, CNPP and surgery alone group, respectively. Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation. Mortality rates of each group were 4% (2/48), 0% (0/44) and 4% (2/47) in the CHPP, CNPP and surgery alone group, respectively. Overall 5-year survival rates of CHPP, CNPP and surgery alone groups were 61%, 43% and 42%, respectively. In a subset analysis, patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion. However, chemonormothermic peritoneal perfusion had no survival benefit. By analyzing with Cox proportional hazard model, chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival. Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion. CONCLUSIONS: Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer, and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor.
Chemotherapy, Adjuvant↗