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Biomedical subjects

Y Uno

Publications and source records attributed to Y Uno.

At least 19 recordsLinked to original sources

Immunization with the Candida albicans membrane fraction and in combination with fluconazole protects against systemic fungal infections.

We studied the immunogenicity of a membrane fraction prepared from Candida albicans cells called C. albicans membrane antigen (CMA). The present study revealed that CMA immunization has antifungal activity in mouse models of systemic fungal infection. Immunization of mice by subcutaneous injections of CMA with incomplete Freund adjuvant induced resistance to infections caused not only by C. albicans but also by Aspergillus fumigatus. The level of resistance to candidiasis was as high as that induced by whole-cell immunization. The acquired resistance to candidiasis in the mice immunized with CMA was not diminished by immunosuppressive treatment with cyclophosphamide. The level of resistance to fungal infections was superior to that given by fluconazole (FLC) treatment alone and highly enhanced by the combination with FLC. When CD4(+) cells in CMA-immunized mice were depleted by a monoclonal antibody, the antifungal activity induced by the combination of CMA and FLC was significantly reduced. These results indicate that immunization with CMA is useful for preventing systemic fungal infections and in combination with FLC for increasing resistance after infection.

Animals

Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.

A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.

Animals

Procarbazine genotoxicity in the MutaMouse; strong clastogenicity and organ-specific induction of lacZ mutations.

Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.

Animals

Thermally reversible xyloglucan gels as vehicles for oral drug delivery.

The potential, as sustained release vehicles, of gels formed in situ following the oral administration of dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed has been assessed by in vitro and in vivo studies. Aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed rigid gels at concentrations of 1.0 and 1.5% w/w at 37 degrees C. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degrees C at pH 6.8. Plasma concentrations of indomethacin and diltiazem, after oral administration to rats of chilled 1% w/w aqueous solutions of the enzyme-degraded xyloglucan containing dissolved drug, and a suspension of indomethacin of the same concentration were compared. Constant indomethacin plasma concentrations were noted from both formulations after 2 h and were maintained over a period of at least 7 h. Bioavailability of indomethacin from xyloglucan gels formed in situ was increased approximately threefold compared with that from the suspension. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for oral delivery of drugs.

Administration, Oral

The role of a staged approach for high-risk Fontan candidates.

The preoperative risk characteristics and surgical outcome were reviewed in 24 patients who underwent a one-stage Fontan procedure (One-stage Group) and in 16 patients who underwent bidirectional cavopulmonary shunt as an interim procedure prior to a subsequent Fontan procedure (Two-stage Group) to clarify the role of the staged approach for high-risk Fontan candidates. There were 2 hospital deaths after the one-stage Fontan, and another 2 after the takedown of the fenestrated Fontan to BCPS in patients considered to be less than ideal candidate because of the presence of 3 or more risk factors. In contrast, among the total of 16 patients in the Two-stage Group who had significantly more risk factors than those in One-stage Group (2.8 +/- 1.4, vs 1.1 +/- 1.2 p < 0.001), 14 patients survived after bidirectional cavopulmonary shunt, and a subsequent Fontan procedure was accomplished in 12 patients of these 14, with 2 operative deaths after the takedown to bidirectional cavopulmonary shunt. The rate of final Fontan completion in the Two-stage Group (10/16, 62.5%) was considered to be reasonable, considering the fact that this patient group essentially includes non-Fontan candidates. Additionally, in the category of high-risk with 3 or more risk factors, the rate of successful Fontan completion was higher in the Two-stage Group than in the One-stage Group (50% vs 25%). In the survivors of the Two-stage Group, the average number of risk factor decreased from 2.7 +/- 1.3 (range 0 to 5) to 1.0 +/- 1.0 (range 0 to 4) after bidirectional cavopulmonary shunt with concomitant procedures (i.e., extended pulmonary artery reconstruction in 8, and repair of atrioventricular valve regurgitation in 4), predominantly due to improved Fontan candidacy, relating to pulmonary and/or ventricular characteristics, and eliminated anatomical risks. In conclusion, the two-stage approach with bidirectional cavopulmonary shunt accompanied by concomitant repair of associated anomaly may be useful to lower the risk enough to allow subsequent Fontan completion in high-risk patients.

Adolescent

A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits.

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.

1-Deoxynojirimycin

Case report: mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging.

A case of mucinous cholangiocarcinoma (CC), a rare histological type of CC, featuring unusual images is reported. The patient was hospitalized because of acute development of jaundice and fever. Computed tomography demonstrated multiple cystic lesions in the liver and a band-like low density area parallel to the intrahepatic portal vein, a so-called 'periportal collar'. Endoscopic cholangiography revealed a stricture of the hepatic duct with slight upstream dilatation. Cytology of the bile juice and fine-needle aspiration of the cystic lesion in the liver disclosed mucinous carcinoma. The patient died of multiorgan failure 3 weeks after admission. The autopsied liver showed that multiple mucus lakes were lined with adenocarcinoma cells and signet ring cells were floating in the mucus lakes. The cancer cells had spread along the portal tract and invaded into the hepatic parenchyma.

Adenocarcinoma, Mucinous

Correlation of lifting versus non-lifting and microscopic depth of invasion in early colorectal cancer.

BACKGROUND: The non-lifting sign is considered a contraindication to endoscopic resection. Our objective was to investigate whether lifting or nonlifting of a lesion is determined by the volume of normal submucosal tissue. METHODS: We measured the thickness of the submucosa and examined the relation between submucosal invasion and lesion elevation induced by submucosal injection in 60 patients with colorectal cancer with evidence of submucosal invasion. Extent of tumor elevation was classified into two groups: A, lifting; B, non-lifting. Submucosal invasion was classified as sm1, sm2, or sm3. The distance between the carcinoma and the line of resection and that between the carcinoma and the muscularis propria were measured. RESULTS: Of 31 sm1 lesions, 29 (93.5%) were group A. All 6 sm3 lesions were group B. All lesions in group A had a value for the distance between carcinoma and muscularis propria of more than 1000 microm. Group B lesions with sm3 invasion had distances of only 105 to 750 microm. CONCLUSION: Lesions classified as sm3 do not elevate in response to submucosal injection, and lesions that become elevated on injection can be resected endoscopically because they are sm1 or sm2 and have a thickness of normal submucosa of more than 1000 microm.

Adenomatous Polyps

[Combination effect of fosfomycin otic solution and norfloxacin against chronic otitis media].

Studies on a combination therapy of fosfomycin (FOM) and norfloxacin (NFLX) against chronic otitis media were performed, and the following results were obtained. 1. The fractional inhibitory concentration index (FIC index) < or = 0.5 between FOM and NFLX showed 66.7% (4/6) against S. aureus isolated from chronic otitis media and 80.5% (4/5) against P. aeruginosa. 2. Clinical effects was excellent in 2 cases (18.2%), good in 6 cases (54.5%) and poor in 3 cases (27.3%). 3. Bacteriologically 9 strains out of 11 patients were eradicated after the combination treatment; 5/6 in S. aureus and 4/5 in P. aeruginosa. 4. No adverse effect and abnormal laboratory findings were observed in this study. It is suggested that the combination of FOM otic solution and NFLX is useful for the treatment of chronic otitis media.

Administration, Oral

Quantitative examinations of internal representations for arm trajectory planning: minimum commanded torque change model.

Quantitative examinations of internal representations for arm trajectory planning: minimum commanded torque change model. A number of invariant features of multijoint planar reaching movements have been observed in measured hand trajectories. These features include roughly straight hand paths and bell-shaped speed profiles where the trajectory curvatures between transverse and radial movements have been found to be different. For quantitative and statistical investigations, we obtained a large amount of trajectory data within a wide range of the workspace in the horizontal and sagittal planes (400 trajectories for each subject). A pair of movements within the horizontal and sagittal planes was set to be equivalent in the elbow and shoulder flexion/extension. The trajectory curvatures of the corresponding pair in these planes were almost the same. Moreover, these curvatures can be accurately reproduced with a linear regression from the summation of rotations in the elbow and shoulder joints. This means that trajectory curvatures systematically depend on the movement location and direction represented in the intrinsic body coordinates. We then examined the following four candidates as planning spaces and the four corresponding computational models for trajectory planning. The candidates were as follows: the minimum hand jerk model in an extrinsic-kinematic space, the minimum angle jerk model in an intrinsic-kinematic space, the minimum torque change model in an intrinsic-dynamic-mechanical space, and the minimum commanded torque change model in an intrinsic-dynamic-neural space. The minimum commanded torque change model, which is proposed here as a computable version of the minimum motor command change model, reproduced actual trajectories best for curvature, position, velocity, acceleration, and torque. The model's prediction that the longer the duration of the movement the larger the trajectory curvature was also confirmed. Movements passing through via-points in the horizontal plane were also measured, and they converged to those predicted by the minimum commanded torque change model with training. Our results indicated that the brain may plan, and learn to plan, the optimal trajectory in the intrinsic coordinates considering arm and muscle dynamics and using representations for motor commands controlling muscle tensions.

Adult

Role of apoptosis in the disappearance of infiltrated and proliferated interstitial cells after myocardial infarction.

Myocardial infarction (MI) progresses from the acute death of myocytes and the infiltration of inflammatory cells into granulation, followed by scars. During the healing process, the myocardial interstitial cell population in the infarcted tissues increases markedly and then decreases. We postulated that apoptosis is responsible for this process. Twenty-four male Japanese white rabbits underwent a 30-minute occlusion of the left coronary artery followed by reperfusion for 2 days, 2 weeks, or 4 weeks (n=8 each). The histological features consisted of dead cardiomyocytes and marked leukocyte infiltration at 2 days after MI and granulation consisting of numerous alpha-smooth muscle actin-positive myofibroblasts, macrophage antigen-positive macrophages, and neovascularization at 2 weeks. At 4 weeks, the cellularity decreased markedly, and scars were evident. Interstitial cells with positive nick end labeling were significantly more frequent at the light microscopic level in the 2-day MI samples (5.3+/-3.6% in the center and 6.9+/-3.3% in the periphery of the infarct region) than in the 2-week (2.5+/-1.0%) and 4-week (0.5+/-0.5%) samples. DNA electrophoresis showed a clear ladder in tissues from the ischemic areas at 2 days after MI but not at 2 and 4 weeks after MI. Ultrastructurally, typical apoptotic figures, including apoptotic bodies and condensed nuclei without ruptured plasma membranes, were detected in leukocytes from all hearts with 2-day MI and in myofibroblasts, endothelial cells, and macrophages from all hearts with 2-week MI. In the electron microscopic in situ nick end labeling, immunogold particles intensely labeled the condensed chromatin of the typical apoptotic nuclei. These particles were also accumulated on nuclei of the interstitial cells showing homogeneous density but not definite condensation as typical apoptotic nuclei, suggesting an early stage of apoptosis. Thus, apoptosis plays an important role in the disappearance of both the infiltrated leukocytes and the proliferated interstitial cells after MI. This finding may have therapeutic implications for postinfarct ventricular remodeling through apoptosis handling during the healing stage of MI.

Animals

N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly reduced infarct size in rabbit hearts.

BACKGROUND: N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase of glycogen-debranching enzyme in the liver, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Because the reduction of the glycogenolytic rate may be one of the mechanisms of myocardial protection in ischemic preconditioning, the compounds inhibiting myocardial alpha-1,6-glucosidase may be protective against ischemic damage. Thus, we investigated whether MOR-14 could inhibit alpha-1,6-glucosidase and reduce the infarct size in rabbit hearts without collateral circulation. METHODS AND RESULTS: MOR-14 dose-dependently decreased the alpha-1,6-glucosidase activity in rabbit heart extract. A tracer study demonstrated the myocardial uptake of a considerable amount of MOR-14 sufficient to fully inhibit alpha-1,6-glucosidase. To assess the infarct size-reducing effect of MOR-14, 54 rabbits were subjected to 30-minute coronary occlusion followed by 48-hour reperfusion. Preischemic treatment with 25, 50, and 100 mg/kg of MOR-14 dose-dependently reduced the infarct size (to 26+/-4%, 19+/-3%, and 14+/-2% of the area at risk, respectively), compared with the saline control (45+/-5%) without altering the blood pressure or heart rate. Another 40 rabbits given 100 mg of MOR-14 or saline 10 minutes before ischemia were euthanized at 10 or 30 minutes of ischemia for biochemical analysis. MOR-14 decreased the alpha-1,6-glucosidase activity to approximately 20% in vivo, reduced the glycogen breakdown, and attenuated the lactate accumulation at both 10 and 30 minutes of ischemia. CONCLUSIONS: Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation of lactate, and reduced the myocardial infarct size by 69%. This cardioprotective effect was independent of changes of blood pressure and heart rate or regional blood flow. It may be associated with alpha-1,6-glucosidase inhibition, because MOR-14 markedly decreased the alpha-1,6-glucosidase activity in the heart.

1-Deoxynojirimycin

[Clinical advantages and myocardial protection of normothermal CPB--comparison with hypothermal CPB].

We studied the clinical advantages and myocardial protection of normothermal CPB with comparing to hypothermal CPB. 22-cases of adult CABG were classified under two groups, according to the temperature of CPB. (Normothermal group: 37 degrees C, Hypothermal group: 32 degrees C) In both groups, the assistant CPB time after aortic declamp, the use of cardioversion that meaned the spontaneous recovery to sinus rhythm appeared or not, the dose of cathecholamines in- and post-operation, and the amounts of postoperative bleeding (after 6 h and 12 h) were compared as the clinical results and the data of CPK-MB, Myocin LC-II, and Troponin-T were measured as the effects of myocardial protection. The method of myocardial protection was the intermittent antegrade cold blood cardioplegia with terminal warm blood for all cases. As a result, the assistant CPB time after aortic declamp, the use of cardiovasion, and the amounts of postoperative bleeding (both of 6 h and 12 h) were less in normothermal group rather than in hypothermal group. (p < 0.05). However we had no differences about the dose of cathecholamines in post-operation and the data of three items between two groups. So, it suggests that the sufficient effects of myocardial protection could be obtained in normothermal CPB as in hypothermal CPB. Therefore we conclude that normothermal CPB could provide some clinical advantages, such as shortening CPB time, recovery of sinus rhythm, and prevention of postoperative bleeding, compared to hypothermal CPB and sufficient myocardial protection.

Blood Loss, Surgical

Farewell to bacteremia caused by endoscopic injection--effectiveness of a new injection catheter with a covered tip.

BACKGROUND: Endoscopic injection has recently been reported as effective for several treatments. Because the common channel (suction and biopsy) is usually contaminated with aspirated gastrointestinal juice containing bacteria, often the tip of the injector needle is also. We report a new catheter needle with a covered tip designed to prevent bacteremia from endoscopic injection. METHODS: The new covered needle catheter (Clisco needle) has a 23-gauge retractable needle with a 3 mm extrusion in one lumen. Its distal tip is covered with rubber, blocking infiltration of contaminated gut juice. Ten of these catheters and 10 other disposable needles were inserted through the colonoscope's biopsy channel for 10 patients. Needle tips were cut off after extrusion, and bacteria cultured were counted by standard plate count method. RESULTS: All cultures from ordinary needles grew Escherichia coli, whereas only 3 new needles grew E. coli. Average counts of bacteria cultured from these 3 catheters and 10 disposable needles were 1-250 and 90-6.1 x 10(6), respectively. The difference was highly significant (p < 0.0001). CONCLUSIONS: This new covered needle catheter reduces contaminating bacteria in patients who require endoscopic injection and may prevent bacteremia without antibiotic prophylaxis.

Bacteremia

Adaptive internal model of intrinsic kinematics involved in learning an aiming task.

The elbow-joint angle and the shoulder-joint angle of participants aiming at targets were multiplied in an experiment that used a position-recording system and a cathode-ray tube screen. The linear transformation in joint angles (intrinsic coordinates) corresponded to a nonlinear transformation between the hand coordinates and the screen coordinates (extrinsic coordinates). We examined whether participants could learn this transformation in the intrinsic coordinates or in the extrinsic coordinates by investigating intermanual (between-hands) transfer under an intrinsically consistent condition and an extrinsically consistent condition. Positive intermanual transfer was observed in the former condition but not in the latter condition. Results suggest that participants can learn the linear transformation in joint angles under the intrinsic coordinates and that the central nervous system adaptively represents the intrinsic kinematics.

Adaptation, Psychological