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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 199 records · Page 11Linked to original sources

Efficacy of a bioreactor filled with porcine hepatocytes immobilized on nonwoven fabric for ex vivo direct hemoperfusion treatment of liver failure in pigs.

We developed a new bioreactor for a bioartificial liver filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF) and in our previous study showed that this NWF bioreactor has promising in vitro efficiency. In the present study, we investigated the efficacy of the NWF bioreactor in a direct hemoperfusion experiment conducted to treat pigs with liver failure. Porcine hepatocytes were isolated from the whole liver of a Sangen strain pig. They were immobilized in a 200 ml column containing NWF via perfusion in a closed circuit for 24 h to prepare a NWF bioreactor. The following day an operative liver failure model was produced by creating a portocaval shunt and ligating the entire hepatoduodenal ligament in the porta hepatis. Perfusion treatment was initiated 4 h after operative induction of liver failure and continued for about 1 h. The pigs which underwent perfusion treatment showed significant improvements in survival and blood data, including ammonia, total bile acid, glucose, and prothrombin time, attributed to significant improvements in the post- as compared to the prebioreactor levels in the perfused blood of the treated pigs. These beneficial effects of the NWF bioreactor were based on its excellent composition which allows the accommodation of adequate numbers of hepatocytes and direct contact between hepatocytes and perfused blood.

Ammonia↗

Characterization of murine CD70 by molecular cloning and mAb.

CD27, a member of the tumor necrosis factor (TNF) receptor family, has been implicated in T cell activation, T cell development and T-dependent antibody production by B cells. Its ligand CD70 has been identified only in humans, and, thus, physiological and pathological roles of the CD70-CD27 interaction remain to be determined in an experimental animal system. In the present study, we identified murine (m) CD70 by molecular cloning, and characterized its expression and function by generating an anti-mCD70 mAb. The mCD70 cDNA encoded a type II transmembrane glycoprotein of the TNF family, having 56.5% identity to the human CD70 amino acid sequence. The mCd70 gene was assigned in the central region of chromosome 17. To explore the expression and function of mCD70, we generated cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein (mCD27-Ig) to mCD70 transfectants. FR70, as well as mCD27-Ig, immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70 far more efficiently than mCD27-Ig. FR70 also abrogated the CD28-independent co-stimulatory activity of A20 cells. The expression of mCD70 was detected on splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti-IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced mCD70 expression on splenic B cells. These results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system. FR70 will be useful for further investigating the physiological and pathological roles of the CD70-CD27 interaction in T cell development, T-dependent antibody production and various disease models in the murine system.

Amino Acid Sequence↗

Outcome of local excision for locally invasive rectal carcinomas with special reference to histological features at the invasive margin.

BACKGROUND: Several researchers reported promising results that local excision with or without postoperative chemo-radiation therapy is an alternative approach for sphincter preservation in patients with locally invasive rectal carcinomas. However, indications and long-term results have not yet been determined. METHODS: Demographic and pathological characteristics of eight patients with locally invasive tumors undergoing initially local excision were reviewed with reference to histological features at the invasive margin. RESULTS: All the tumors were well differentiated adenocarcinomas. In all but two tumors, the invasion was limited within the proper muscle layer. Radiation therapy was given preoperatively in one patient and postoperatively in two patients. Additional bowel resection was not attempted in these three cases. Among the remaining five patients, two received additional bowel resection with lymph node dissection. No lymph node metastasis was observed in these two patients. During the average follow-up period of 55 months, three patients had regional lymph node metastases at 7, 36 and 72 months, respectively. Another patient had regional lymph node and distant metastases at 5 months. Three out of five patients with moderate to severe grade of dedifferentiated histology at the invasive margin (H-inv) had regional lymph node metastases. On the other hand, one out of three patients with mild H-inv had lymph node metastases. CONCLUSIONS: H-inv may be useful as a clinical predictor of lymph node metastasis. However, more experience is needed to confirm the usefulness of H-inv in selecting invasive rectal cancer patients in whom local excision is safe and appropriate.

Adenocarcinoma↗

Characteristics in primary signet-ring cell carcinoma of the colorectum, from clinicopathological observations.

BACKGROUND: The biological behavior of signet-ring cell carcinomas in colorectum tends to be worse than that of mucinous carcinomas. However, in previous studies, clinicopathological features of this disease have been somewhat ill-defined because various histological criteria of this disease were adopted. METHODS: We selected 11 cases of signet-ring cell carcinomas and 29 cases of mucinous carcinomas among 1595 consecutive colorectal carcinomas on defined criteria and compared clinicopathological and molecular biological features between these two types of carcinomas. RESULTS: Clinical staging of signet-ring cell carcinomas were far advanced and their prognosis tended to be worse than that of mucinous carcinomas. Furthermore, the incidence of K-ras mutations in signet-ring cell and mucinous carcinomas showed no difference between these two types of carcinomas. However, the incidence of K-ras mutation in these diseases was slightly lower than that in 30 ordinary colorectal carcinomas examined as a comparison. CONCLUSIONS: These results suggest that the carcinogenesis of signet-ring cell and mucinous carcinomas are different from that of ordinary colorectal carcinomas and that there may exist other genes related to malignancy of signet-ring cell carcinomas.

Adenocarcinoma, Mucinous↗

Microsatellite instability is associated with the macroscopic configuration of neoplasms in patients with multiple colorectal adenomas.

BACKGROUND: The management of patients with multiple colorectal adenomas, 10-100 in number, is often troublesome clinically. To establish the reasonable management of such cases, genetic backgrounds should be made clear. METHODS: For a total of 19 adenomas and four carcinomas from four patients with multiple colorectal adenomas, we analyzed genetic instability at four selected microsatellite loci and screened exon 1-4 of the APC gene with special reference to macroscopic configurations of adenomas and carcinomas. RESULTS: RER-positive phenotypes were detected in none of 13 protruded type adenomas, two (33%) out of six superficial elevated type adenomas and two (50%) out of four carcinomas. We detected no mutation of exon 1-4 of the APC gene in any sample. In patients with multiple colorectral adenomas, the proportion of superficial elevated type adenomas exhibiting genetic instability was significantly higher than that of protruded type adenomas. CONCLUSIONS: The results suggested that RER-positive phenotype was an early event in tumorigenesis through superficial elevated type adenomas.

Adenoma↗

Defect in an intrahepatic degradation of apolipoprotein B in suncus: an animal model of hypobetalipoproteinemia.

We have previously shown that fatty liver is easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) is very low. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is almost absent in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembly process of apo B-containing lipoproteins, leading to a low level of plasma apo B. Another possible explanation for the induction of fatty liver in suncus is a defect in apo B-processing in the liver. In this study, we investigated the hepatic synthetic rate and intrahepatic degradation of apo B using primary cultured hepatocytes derived from suncus and rats. In order to estimate intrahepatic degradation of apo B, we added N-acetylleucyl-leucynorleucinal to the culture medium as an inhibitor of apo B degradation. The basal synthesis of apo B in suncus hepatocytes was 50% of that in rat. Intracellular degradation of apo B was not observed in suncus hepatocytes, while it was obvious in rat hepatocytes. This evidence suggests that the lower secretion rate of apo B lipoprotein is not due to the intrahepatic degradation of apo B, but may be due to the low synthetic rate of apo B.

Animals↗

Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.

OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.

Animals↗

Growth hormone and insulin-like growth factor I augment bactericidal capacity of human polymorphonuclear neutrophils.

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on bactericidal capacity of human polymorphonuclear neutrophils (PMNs) were investigated. Venous blood was collected from healthy volunteers. In Experiment 1, PMNs were isolated, incubated with GH or IGF-I, and cocultured with Escherichia coli. E. coli-killing capacity, viability, and CD11b and CD16 expressions of PMNs were then assessed. Both GH and IGF-I enhanced E. coli killing by PMNs. GH preserved PMN viability during E. coli killing, whereas IGF-I enhanced PMN CD11b expression before coculture with E. coli. In Experiment 2, whole blood was washed and incubated with GH or IGF-I. PMNs in washed whole blood were then analyzed for phorbol myristate acetate (PMA)-stimulated CD11b, CD35, and CD16 expressions and production of reactive oxygen intermediates (ROI), as well as phagocytosis with/without anti-CD11b antibody. IGF-I enhanced PMN expressions of CD11b and CD35, but not CD16, stimulated with PMA. Both hormones enhanced phagocytosis, which was abrogated by anti-CD11b antibody, and intracellular ROI production by PMNs. These results indicate that both GH and IGF-I augment human PMN bactericidal capacity, via increased phagocytosis and intracellular ROI production. Preservation of PMN viability by GH and enhanced complement receptor expression by IGF-I may also be associated with augmented PMN bactericidal capacity. Although PMN activation has potentially harmful aspects, these results encourage additional studies to confirm the clinical relevance of exogenous GH or IGF-I for the prevention or management of septic complications in perioperative or critically ill patients especially with low circulating GH and/or IGF-I levels.

Cell Survival↗

Epidemiological study of a food-borne outbreak of enterotoxigenic Escherichia coli O25:NM by pulsed-field gel electrophoresis and randomly amplified polymorphic DNA analysis.

This study investigated the applicability of molecular epidemiological techniques to the identification of the causal agent of an outbreak of diarrhea caused by ingestion of food contaminated with enterotoxigenic Escherichia coli (ETEC). The outbreak occurred at four elementary schools in July 1996 and affected more than 800 people. Illness was most strongly associated with eating tuna paste (relative risk, 1.79; 95% confidence interval = 1.16 to 2.79; P = 0.0001). To evaluate the epidemiological characteristics of the pathogen, the DNAs from numerous isolated ETEC strains were subjected to randomly amplified polymorphic DNA analysis, pulsed-field gel electrophoresis of nuclease S1-treated plasmid DNA, and analysis of genomic DNA restriction fragment length polymorphisms. All ETEC isolates were of the O25:NM (nonmotile) serotype, which carries a heat-stable enterotoxin Ib gene. Genotypic analysis demonstrated that the strains isolated from the patients at all four schools were identical. The isolates of ETEC O25:NM obtained from the tuna paste that had been served for lunch at these schools were genetically indistinguishable from those isolated from the patients. Results suggest that this outbreak was food borne. The molecular biology-based epidemiological techniques used in this study were useful in characterizing the causal agent in this food-borne epidemic.

Animals↗

[NK cell activity and subsets of truck drivers along with related factors].

We investigated the immunity and the main factors that affect the immune system of 19 truck drivers as the experimental group and 27 office workers as the control group at a transit corporation in Tokyo; all subjects in both groups were examined through an assay of NK activity and NK subsets before and after work. At the same time, they were asked to complete a questionnaire on their working hours per day (WHPD) and driving hours per day (DHPD), in addition to the Health Practice Index (HPI), Self-Rating Depression Scale (SDS), Stress Tolerance Check List (STCL), and Symptom Checklist (SCL). The results obtained were as follows: 1. Before work, no difference was seen in NK activity between the experimental group and the control group, with both groups showing E:T ratios 5:1 to 20:1. After work, the NK activity (E:T = 20:1) of the experimental group was significantly lower than that of the control group. 2. In the experimental group, the NK activity and NK subsets (CD3-CD16+CD56+, CD3-CD56+, CD3-CD16+) of the peripheral blood lymphocytes after work were significantly lower than before work (p < 0.05, p < 0.01, p < 0.01). After more than five driving hours, the value of the CD3-CD16+CD56+ subset was significantly lower than that after fewer driving hours. 3. Correlation coefficients were calculated based on the average value of NK activity (E:T = 20:1), CD3-CD16+CD56+ subset, and WHPD, DHPD, and HPI in the driving group. NK activity (E:T = 20:1) and DHPD were found to be negatively correlated (r = -0.28), as were the CD3-CD16+CD56+ subset and WHPD (r = -0.43) and the CD3-CD16+CD56+ subset and DHPD (r = -0.63). On the other hand, NK activity (E:T = 20:1), the CD3-CD16+CD56+ subset and HPI were found to be positively correlated (r = 0.41 and 0.33).

Adult↗

Evaluation of a smoking cessation program implemented in the workplace.

This paper evaluates the effectiveness of a smoking cessation program, known as "Smoke Busters." A quasi-experimental design was used. The experimental group consisted of 35 workers (33 males and 2 females) who smoked and volunteered to take part in the program held at a chemical company. Thirty five age-, sex-, and job category-matched smokers who did not participate in the program were used as controls. The program consisted of 6 sessions held over a period of 6 months. The sessions were organized in a workshop style, with 6 groups, each consisting of 5-6 participants, meeting for 2 hr during working hours. The effectiveness of the program was evaluated by the abstinence rate among the participants at one year after the start of the program. The abstinence rates of the experimental group and control group were 22.9% and 5.7%, respectively. Thus net abstinence rate was 17.2%. Given that 13% is considered as a reasonable benchmark for assessing the effectiveness of smoking cessation programs based on the results of the studies conducted in North America, one-year abstinence rate of 17% in this study, though not statistically significant (0.05 < p < 0.1) encourages larger experiments.

Adult↗

Quantitative analysis of the cyclin expression in human esophageal cancer cell lines.

To study the altered mechanisms of cell cycle regulation in esophageal cancer, the expressions of cyclins involved in G1/S transition were analyzed in a series of 26 human esophageal cancer cell lines. To evaluate and compare the levels of cyclin expression, flow cytometric analysis was performed using human lymphocytes as control. Increased expressions of cyclin A, D1, D3 and E were found in 23.1% (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines, respectively. All cell lines studied expressed less cyclin D2 than lymphocytes and the majority of the cell lines expressed cyclin D3 at levels similar to those of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E. Expressions of cyclin D1 and E were significantly elevated as compared to those of cyclin A, D2 and D3. These results suggest that increased expressions of the positive cell cycle regulators cyclin D1 and E may play an important role in esophageal carcinogenesis.

Biomarkers, Tumor↗

Unilateral arterial reconstruction for aortoiliac occlusive disease.

METHODS: The outcomes of 234 arterial bypasses for aortoiliac occlusive disease were retrospectively analyzed. Surgical procedures included 60 bilateral aorto-/iliofemoral bypasses, 140 unilateral aorto-/iliofemoral bypasses, and 34 femorofemoral cross-over bypasses. Nineteen patients (13.6%) showed deterioration of the contralateral iliac artery after the initial unilateral operation. Of these patients, 11 patients underwent further surgical treatments; including 5 unilateral aortofemoral operation bypasses, 2 iliac thromboendarterectomies, 2 iliac PTA's, 1 femorofemoral bypass, and 1 bilateral aortofemoral bypass. The remaining 8 patients received conservative treatment because of their risk factors. The patency rate of the unilateral reconstruction has improved during the last 12 years according to our historical analysis. RESULTS: Our results demonstrate that unilateral vascular reconstruction is a valuable alternative to conventional bilateral reconstruction in unilateral symptomatic aortoiliac occlusive disease. CONCLUSIONS: Accurate preoperative diagnosis and early detection of the progression of sclerotic lesions on the contralateral side are the keys to successful results.

Aorta↗

Risk factors for restenosis after balloon angioplasty in focal iliac stenosis.

BACKGROUND: The risk factors for restenosis after angioplasty have not yet been established because of the inconsistencies among treated lesions, differences in the techniques used, and variable end points. We evaluated the predictive variables relating to postangioplasty restenosis. METHODS: One hundred sixty-one transluminal balloon angioplasties were studied in 138 consecutive patients with focal iliac arterial stenosis (< or = 4 cm) caused by arteriosclerosis between January 1981 and December 1995. Restenosis was diagnosed on the basis of recurrent symptoms associated with an apparent drop in the ankle-brachial pressure index and angiographic visualization of restenosis. RESULTS: Being younger than 60 years (risk ratio 2.585) and poor runoff (risk ratio 2.328) were found to be important variables predicting restenosis by the Cox regression model. The restenosis-free patency rates were significantly better in patients older than 60 years of age (p = 0.0242), with good distal runoff (p = 0.0487), and without diabetes (p = 0.0111). CONCLUSIONS: Being younger than 60 years of age and poor distal runoff are important predictors of restenosis after iliac balloon angioplasty.

Adult↗

[Risk factors in aged patients undergoing gastrointestinal cancer operations].

With the rapid increase in the elderly population in Japan and the continued advances in perioperative management and operative techniques, more surgical procedures will be performed in the geriatric patients. The loss of reserve capacity and associated disease in the elderly patients may lead to an inappropriate response to surgical stress, resulting in high morbidity and mortality. Therefore, the identification of surgical risk is imperative in the surgical care of aged patients. The risk factors in the aged include malnutrition, anemia, cerebrovascular disease, hepatic disorders and immunosuppressive therapy. This review focuses on the risk factors and simple method to estimate the surgical risk in aged patients undergoing gastrointestinal cancer surgery.

Aged↗

[Colorectal carcinogenesis: a historical review].

In view of the changing concepts of colorectal carcinogenesis during the past 20 years, a historical review of colorectal carcinogenesis is presented. The concept of colorectal carcinogenesis is presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neomaterials; and 4) carcinogenesis based on molecular biology. In the first period, large adenomas were thought to play the most important role as precursors of colorectal carcinomas. The concept was referred to as the "adenoma-carcinoma sequence." However, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The natural history of colorectal neoplasms revealed morphological changes from polypoid or sessile lesions to ulcerating carcinomas during a varying time span. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on new precursors of colorectal carcinomas that had not been recognized in the past. They tend to have a much higher malignant potential than polypoid neoplasms. Molecular biology clarified the absence 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. The concept referred to as the "adenoma-carcinoma sequence" changed because colonoscopic polypectomy specimens were studied, and rather small nonpeduculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolyoid neoplasms provided us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms. Carcinogenesis of so-called de novo carcinoma should be explained on a molecular basis. When sequential multistep genetic alterations take place very rapidly the carcinoma seems to arise de novo. Until the gene responsible for real de novo carcinoma is detected, the term de novo-type carcinoma should be used.

Adenoma↗

[Clinical result of intraperitoneal hyperthermic chemoperfusion for gastric cancer with serosal invasion to prevent peritoneal recurrence].

In order to evaluate clinical effects of intraperitoneal hyperthermic chemoperfusion (IHCP) to prevent peritoneal recurrence in gastric cancer patients with serosal invasion, the clinical outcome was studied in 126 gastric cancer patients with macroscopic serosal invasion. Results of 59 patients who had surgery combined with IHCP (IHCP group) were compared with those of 67 patients who had surgery alone (control group). IHCP was performed for 120 minutes just after surgery under hypothermic general anesthesia with perfusate containing 10 micrograms/ml of mitomycin C. The inflow temperature and the outflow temperature of the perfusate were controlled to be 44.5 approximately 45 degrees C, and 43 approximately 44 degrees C, respectively. The 2-, 4- and 8-year survival rates for the IHCP group were 86%, 74% and 66%, respectively, against 78%, 59% and 50%, respectively, in the control group. The survival rates of the IHCP group were significantly better than those of the control group. Peritoneal recurrences after surgery were encountered in one of 59 patients in the IHCP group and 17 of 67 patients in the control group. The peritoneal recurrence rate of the IHCP group was significantly lower than that of the control group. These results suggest that IHCP treatment is effective in prevention of peritoneal recurrences after surgery for gastric cancer patients with serosal invasion.

Antibiotics, Antineoplastic↗