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Biomedical subjects

T Furuno

Publications and source records attributed to T Furuno.

At least 37 records · Page 2Linked to original sources

Is suprapubic cystostomy an optimal urinary management in high quadriplegics?. A comparative study of suprapubic cystostomy and clean intermittent catheterization.

INTRODUCTION: Long-term outcome of spinal cord injury (SCI) patients was compared between those managed by suprapubic cystostomy (SPC) and clean intermittent catheterization (CIC) with particular emphasis on an incidence of urinary tract complications and patients perception for urinary management. MATERIALS AND METHODS: The study comprised 61 SCI patients; 34 patients managed with SPC (group A), while 27 with CIC (group B). After stabilization of their condition, all were followed annually on an outpatient basis with clinical history, urinalysis, urinary imaging and renal function studies. Mean follow-up periods were 8.6 and 9.9 years for groups A and B, respectively. Between groups, a comparative study was performed on the incidence of urinary complications such as renal dysfunction, hydronephrosis, vesicoureteral reflux, symptomatic genitourinary infection and urinary stone. Satisfaction with urinary management was also estimated using the questionnaires during follow-up. RESULTS: Renal dysfunction, hydronephrosis and vesicoureteral reflux were not found in either group. Symptomatic genitourinary infection was seen in 4 (12%) of group A and 7 (26%) of group B, respectively. The incidence of renal stone was 3 (9%) in group A and 1 (4%) in group B. A significant difference was not found between two groups in these urinary complications. On the contrary, bladder stone was seen more frequently in group A (65%) than in group B (30%) with a significant difference (p<0.001). The degrees of incontinence, bother score of daily activities, and overall satisfaction showed no significant difference between the two groups. CONCLUSION: Except for bladder stones, SPC is a valuable option of urinary management for quadriplegic patients, the results of which were comparable to paraplegic SCI patients managed with CIC.

Adolescent↗

Efficacy of cholesterol-lowering treatment in Japanese elderly patients with coronary artery disease and normal cholesterol level using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

The clinical benefit of cholesterol-lowering treatment is unknown in the Japanese elderly in whom the prevalence of morbidity and mortality related to coronary artery disease are known to be low. To evaluate the efficacy of cholesterol-lowering treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor in Japanese elderly patients with documented coronary artery disease, 121 patients with serum cholesterol > or = 150 mg/dl prospectively received HMG-CoA reductase inhibitor, and 271 patients undergoing cholesterol-lowering treatment based on dietary therapy alone served as historical controls. The 143 elderly patients age > or = 65 years in the 2 groups had similar baseline serum total cholesterol level (201 +/- 30 vs 202 +/- 31 mg/dl), age (71 +/- 4 vs 70 +/- 4 years), proportion of men (37/53 vs 64/90), number of diseased vessels (1.7 +/- 0.9 vs 1.5 +/- 1.0), and incidences of other classical coronary risk factors, including hypertension, diabetes mellitus, smoking, obesity and family history of coronary artery disease. In all 392 patients, similar trends were observed, including serum total cholesterol level (208 +/- 33 vs 201 +/- 34 mg/dl). With HMG-CoA reductase inhibitors, serum total cholesterol level was reduced by 14% in the elderly subjects and by 13% in all patients. During the follow-up of approximately 3 years, cardiac events occurred in 5 patients (one elderly) in the treatment group and 38 patients (12 elderly) in the control group. Kaplan-Meier survival estimates revealed a higher event-free survival rate with HMG-CoA reductase inhibitors in the elderly subjects (98% vs 85%, p < 0.05) and in all patients (94% vs 86%, p < 0.05). Cox proportional hazard modeling also demonstrated a significant reduction in risk for cardiac events with drug therapy (relative risk 0.32, p < 0.05), in addition to the number of diseased vessels (relative risk 1.8, p < 0.01). In contrast, no additional risk was observed with advancing age. Cholesterol-lowering treatment with HMG-CoA reductase inhibitors is effective to improve the prognosis of Japanese elderly patients, including those with normal serum cholesterol level.

Anticholesteremic Agents↗

Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P.

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. However, whether mast cell activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Addressing this issue, we used an in vitro coculture approach comprising cultured murine superior cervical ganglia and rat leukemia basophilic cells (RBLs; possesses properties of mucosal-type mast cells). Following loading with the calcium fluorophore, Fluo-3, neurite-RBL units (separated by <50 nm) were examined by confocal laser scanning microscopy. Addition of bradykinin, or scorpion venom, dose-dependently elicited neurite activation (i.e., Ca2+ mobilization) and, after a lag period, RBL Ca2+ mobilization. Neither bradykinin nor scorpion venom had any direct effect on the RBLs in the absence of neurites. Addition of a neutralizing substance P Ab or a neurokinin (NK)-1 receptor antagonist, but not an NK-2 receptor antagonist, dose-dependently prevented the RBL activation that resulted as a consequence of neural activation by either bradykinin or scorpion venom. These data illustrate that nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P, operating via NK-1 receptors, is an important mediator of this communication. Our findings have implications for the neuroimmune signaling cascades that are likely to occur during airways inflammation, intestinal hypersensitivity, and other conditions in which mast cells feature.

Animals↗

Nuclear translocation of green fluorescent protein-nuclear factor kappaB with a distinct lag time in living cells.

A highly fluorescent mutant form of the green fluorescent protein (GFP) has been fused to the human nuclear factor kappaB (NF-kappaB) p50 and p105 (p50/IkappaB gamma), a precursor protein of NF-kappaB p50. GFP-p50 and GFP-p105 were expressed in monkey COS-7 cells and human HeLa cells. Translocation of these chimeric proteins was observed by confocal laser scanning microscopy. GFP-p50 (without IkappaB gamma) in the transfected cells resided in the nucleus. On the other hand, GFP-p105 (GFP-p50 with IkappaB gamma) localized only in the cytoplasm before stimulation and translocated to the nucleus with stimulant specificity similar to that of native NF-kappaB/IkappaB. In addition, the translocation of NF-kappaB to the nucleus had a distinct lag time (a quiescent time) in the target cells. The lag time lasted 10-20 min after stimulation with hydrogen peroxide or tumor necrosis factor alpha. It was suggested that this might be due to the existence of a limiting step where NF-kappaB is released from NF-kappaB/IkappaB by the proteasome.

Amino Acid Substitution↗

Grasping forceps assisted endoscopic resection of large pedunculated GI polypoid lesions.

BACKGROUND: Endoscopic resection of pedunculated polyps with heads 1 cm or greater in diameter is technically complex. To facilitate removal of such polyps, we developed grasping forceps assisted endoscopic resection in which we use a detachable snare to prevent polypectomy-related bleeding and evaluated the usefulness and safety of the procedure. METHODS: Ten patients with pedunculated polyps with heads 1 cm or greater in diameter were treated with this technique. A two-channel endoscope, grasping forceps, electrosurgical snare, and detachable snare are needed for the procedure. RESULTS: All lesions were easily and safely resected. During this procedure, a two-channel endoscope with grasping forceps proved to be satisfactory for handling the detachable snare and the electrosurgical snare and for accurate recognition of the stalk under good visual control. No hemorrhage, perforation, or other complication occurred as a result of use of this new technique. CONCLUSIONS: Grasping forceps assisted endoscopic resection of polyps with a detachable snare is an effective method for the prevention of polypectomy-associated bleeding. This technique makes it technically easier to resect large pedunculated polypoid lesions of the GI tract.

Aged↗

Mercuric chloride induces increases in both cytoplasmic and nuclear free calcium ions through a protein phosphorylation-linked mechanism.

The mechanism of the lymphocyte stimulatory action of sulfhydryl group-reactive mercuric ions was studied with respect to its potential ability to induce a protein tyrosine phosphorylation-linked signal for mobilization of free Ca2+ into cytoplasm and nucleus of the cell. Exposure of human leukamic T cell line (Jurkat) cells to high (1 mM) and low (0.01 mM) concentrations of HgCl2 induced tyrosine phosphorylation of multiple proteins in a concentration-dependent manner. Confocal microscopy directly visualized the time course localization of Ca2+ inside the cells after exposure to HgCl2. The onset and level of Ca2+ mobilization following HgCl2 exposure were in parallel to those of protein tyrosine phosphorylation. Interestingly, by either concentration of HgCl2, Ca2+ was mobilized in both cytoplasm and nucleus almost simultaneously, and the level of Ca2+ mobilization in the nucleus was more than that in the cytoplasm. All the HgCl2-mediated Ca2+ mobilization was prevented by addition of protein kinase inhibitor staurosporin prior to HgCl2. These results suggest that heavy metal stress triggers a protein tyrosine phosphorylation-linked signal that leads to a nuclear event-dominant Ca2+ mobilization.

Calcium Signaling↗

Low dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function in dilated cardiomyopathy.

OBJECTIVE: To determine whether dobutamine stress echocardiography can predict the improvement of left ventricular systolic function in patients with dilated cardiomyopathy (DCM). METHODS: Myocardial contractile reserve, as assessed by dobutamine stress echocardiography, was determined in 18 patients with DCM (mean (SD) age 53 (13) years, left ventricular ejection fraction (LVEF) 28 (10)%) and compared with changes in LVEF during a follow up period of 15 (8) months. The LVEF and regional left ventricular wall motion score (0, normal to 4, dyskinesis) of 12 segments in short axis and four chamber views were analysed before and after dobutamine infusion (5-20 microg/kg/min). RESULTS: During a follow up period of 15 (8) months, a significant improvement in LVEF (> 20%) was found in seven patients but not in the remaining 11. Baseline haemodynamic findings were similar in both groups. Patients with an improvement in follow up LVEF showed a greater change in wall motion score from baseline during dobutamine infusion than patients with no improvement (at rest, 1.7 (0.4) v 1.9 (0.2), NS; dobutamine 10 microg/kg/min, 0.6 (0.4) v 1.2 (0.4), p < 0.05). The percentage change in LVEF during dobutamine infusion was also significantly greater in patients who showed improvement than in those who did not. The change in LVEF during the follow up period (follow up LVEF/baseline LVEF) correlated well with the change in LVEF during dobutamine stress (LVEF at rest/LVEF at dobutamine 10 microg/kg/min; r = 0.74, p < 0.001). CONCLUSIONS: Changes in left ventricular systolic performance during low dose dobutamine stress echocardiography are a useful marker to predict the outcome of left ventricular systolic function in patients with DCM.

Adult↗

The relation between degranulation and rapid metabolic responses in RBL-2H3 cells.

The relation between degranulation and rapid metabolic responses (acidification rate changes) in RBL-2H3 cells was studied using a cytosensor microphysiometer, a silicon-based biosensor system. The metabolic responses in RBL-2H3 cells by antigen stimulation were compared with those by inhibitors of Ca2+ -ATPase. The former resulted in a rapid transient increase in the acidification rate of RBL-2H3 cells while the latter resulted in gradual decreases. When RBL-2H3 cells were costimulated with the inhibitors of Ca2+ -ATPase and an activator (PMA, phorbol-12-myristoyl-13-acetate) of protein kinase C, the metabolic responses increased again in RBL-2H3 cells. This seems to indicate that degranulation in RBL-2H3 cells was accelerated by costimulation with the inhibitors and PMA. However, costimulation was not able to completely mimic the way antigen stimulated RBL-2H3 cells in degranulation and in rapid metabolic responses.

Animals↗

Determinants of exercise-induced ST-segment displacement in the aVL lead in patients with known or suspected coronary artery disease.

Although the aVL lead in exercise electrocardiography is reported to be helpful in identifying a significant narrowing of the left anterior descending coronary artery (LAD), its role in exercise testing has not been fully evaluated. Accordingly, 821 patients who underwent both standard exercise testing and coronary angiography were evaluated. In patients with aVL lead ST elevation, the incidence of a significant narrowing of the LAD (124/165 vs 348/656; p<0.001) was higher than in those without. Multiple logistic regression analysis revealed that the 2 most important variables that correlated with aVL lead ST elevation were a greater number of leads with ST depression in the inferior leads and a smaller amplitude of R wave in the aVL lead. In contrast, variables correlating with aVL lead ST depression in the majority of cases were a greater number of leads with ST depression in all leads and the presence of inferior lead ST elevation. The results of this study indicate that although aVL lead ST elevation could be a marker for LAD narrowing, more important factors such as inferior lead ST-segment depression and the R-wave amplitude of the aVL lead should be taken into consideration. In contrast, ST depression in the aVL lead mostly represents exercise-induced myocardial ischemia of greater extent and severity.

Adult↗

Functional recovery after coronary artery bypass grafting in patients with severe left ventricular dysfunction and preserved myocardial viability in the left anterior descending arterial territory as assessed by thallium-201 myocardial perfusion imaging.

To evaluate the functional recovery after coronary bypass surgery in patients with severe left ventricular (LV) dysfunction (ejection fraction (EF) < or = 35%), 100 consecutive patients with viable myocardium in the territory supplied by the left anterior descending artery (LAD) underwent coronary bypass grafting. In addition, cardiac catheterization and single-photon emission computed tomography (SPECT) perfusion imaging with thallium-201 were repeated 1-year postoperatively. Although 12 patients with severe LV dysfunction were preoperatively in a worse New York Heart Association functional class (3.1+/-0.7 vs 2.4+/-0.8; p<0.01), had a higher incidence of heart failure (10/12 vs 14/88; p<0.001) and had a worse LVEF (29+/-5 vs 61+/-14%; p<0.001) compared with 88 patients without severe LV dysfunction, the operative mortality was similar in the 2 groups (1/12 vs 2/88; p=NS). The postoperative NYHA functional class in the patients with severe LV dysfunction was similar to that in the patients without such dysfunction (1.6+/-0.7 vs 1.3+/-0.6; p=NS). In addition, the 1-year postoperative study revealed a significant improvement in the thallium defect score in both the LAD territory (1.7+/-1.2 to 0.7+/-1.0, p=0.01) and all the territories (5.2+/-2.2 to 3.2+/-1.9, p=0.002) in patients with severe LV dysfunction, whereas no improvement in defect score was found in either of these territories in those without severe LV dysfunction (LAD: 0.6+/-1.4 to 0.4+/-1.2, p=NS; All: 1.9+/-2.2 to 1.8+/-2.0, p=NS). Furthermore, a marked 1-year postoperative improvement (15-24%; 95% confidence interval) in LVEF (29+/-5 to 48+/-10%, p<0.001) was demonstrated in patients with severe LV dysfunction, but not in those without such dysfunction (60+/-13 to 61+/-11%, p=NS). These results indicate that myocardial viability in the LAD territory, as demonstrated by thallium-201 SPECT perfusion imaging, predicts a significant improvement in functional class and LVEF of at least 10% or more after coronary artery bypass grafting in patients with severe LV dysfunction.

Adult↗

Activation of caspase-3-like protease by digitonin-treated lysosomes.

Apoptosis, a naturally occurring programmed cell death or cell 'suicide', has been paid much attention as one of the critical mechanisms for morphogenesis and tissue remodeling. Activation of cysteine aspartases (caspases) is one of the critical steps leading to apoptosis. Although a mitochondria-mediated pathway has been postulated to be one of the activation mechanism of caspase-3, another subcellular compartment might be involved in the activation of the enzyme. The present study shows that the supernatant fraction of digitonin-treated lysosomes strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease. Activation of caspase-3-like protease by digitonin-treated lysosomal fractions was specifically suppressed by leupeptin and E-64, inhibitors of cysteine protease. These results indicate that leakage of lysosomal cysteine protease(s) into the cytosolic compartment might be involved in the activation of caspase-3-like protease.

Animals↗

Membrane fusion plays an important role in gene transfection mediated by cationic liposomes.

By confocal laser scanning microscopy (CLSM) we have studied the membrane fusion between cationic liposomes and the endosome membranes involved in gene transfection mediated by cationic liposomes. Antisense oligonucleotides were transferred by cationic liposomes with a cationic cholesterol derivative, cholesteryl-3beta-carboxyamidoethylenedimethylamine (I). Cationic liposomes were made by a mixture of the derivative I and DOPE. The intracellular distribution of fluorescein-conjugated antisense oligonucleotides (phosphorothioate) was studied by CLSM. The images showed that the antisense oligonucleotides were preferentially transferred into the nucleus of target cells (NIH3T3, COS-7 and HeLa cells) by the liposomes with derivative I. However, their transfection was completely blocked by nigericin which was able to dissipate the pH gradient across the endosome membranes, although the liposome/DNA complex was found in the cytoplasm of the target cells. This was quite in contrast with the fluorescence images of the target cells treated with wortmannin, an inhibitor of endocytosis. The results suggest that at least two steps are effective for gene transfection mediated by the cationic liposomes with cationic cholesterol derivatives. One is the endocytosis of the liposome/DNA complex into the target cells and the other is the removal of antisense oligonucleotides (plasmid DNAs) from the complex in the endosomes. The latter step was preferentially preceded by the membrane fusion between the cationic liposomes and the endosome membranes at around pH 5.0.

3T3 Cells↗

Atomic force microscopy for studying gene transfection mediated by cationic liposomes with a cationic cholesterol derivative.

Atomic force microscopy (AFM) was used for studying gene transfection mediated by cationic liposomes which contain a cationic cholesterol derivative with a different spacer arm. Cationic liposomes were made by a mixture of one of eight cationic cholesterol derivatives and 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanolamine (DOPE). AFM images showed that vesicles made of the liposome/DNA complex had various diameters depending on each cationic cholesterol derivative with a different spacer arm. The results showed that the diameter of the liposome/DNA complex was well related to the transfection activity of plasmid pSV2CAT DNA to a cultured cell line (NIH3T3). From the results it was found that the vesicles with moderate diameters (from 0.4 to 1.4 microm) were moste effective for gene transfection of plasmid pSV2CAT DNA into the target cell. Neither smaller vesicles (< 400 nm) nor larger vesicles (> 1.4 microm) were adequate for gene transfection. As the gene transfection by the cationic liposomes was mostly inhibited by wortmannin, an inhibitor of endocytosis, it is suggested that the vesicles with moderate diameters were useful for gene transfection by endocytosis.

3T3 Cells↗

Imaging two-dimensional arrays of soluble proteins by atomic force microscopy in contact mode using a sharp supertip.

A sharp tip with high aspect ratio is required for imaging biological macromolecules by atomic force microscopy (AFM). A tip with the end radius of curvature less than 3 nm has been reproducibly fabricated by means of electron beam deposition (EBD) in a field-emission scanning electron microscope. Two-dimensional protein arrays of ferritin and catalase, prepared at air/water interface and transferred onto silicon wafer, could be imaged both in air and in water by AFM using this sharp EBD-tip in contact mode. The negative staining preparation conventionally used in the transmission electron microscopy of protein was applied and shown to be quite effective in fixing the protein arrays for the AFM imaging in air. Individual molecules of ferritin and catalase were visible in the two-dimensional arrays. Also, imaging in water of these protein arrays presented molecular images clearer than in air, due probably to the absence of the adhesion force and the resulting weak lateral force during scanning. These images convince us of the capability of this supertip for AFM studies of biological molecules under aqueous conditions.

Air↗

Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

Adolescent↗

Release of nitric oxide and expression of constitutive nitric oxide synthase of human endothelial cells: enhancement by a 14-membered ring macrolide.

A 14-membered ring macrolide, erythromycin, acts not only as an antibacterial but also as an anti-inflammatory agent. We have previously reported that erythromycin modulates neutrophil functions and ameliorates neutrophil-induced endothelial cell damage through the action of cyclic AMP-dependent protein kinase (PKA) and nitric oxide (NO). We investigated the effect of erythromycin on human endothelial cell functions. Erythromycin enhanced intracellular calcium ion concentration ([Ca2+]i) of endothelial cells and NO release from endothelial cells. The enhancement of NO release from endothelial cells by erythromycin was abolished by addition of EGTA in the medium and was partially reduced by addition of H-89, an inhibitor of PKA. These results suggest that erythromycin enhances NO release from endothelial cells through the action of PKA and [Ca2+]i. In addition, constitutive NO synthase (cNOS) protein expression of endothelial cells was dose-dependently enhanced by treatment with erythromycin, which might also contribute to the enhancement of NO release from endothelial cells by erythromycin. The effect of erythromycin as an anti-inflammatory agent might be partially mediated through the enhancement of NO release from endothelial cells and the drug might be a useful tool for the investigation of cNOS of endothelial cells.

Anti-Inflammatory Agents↗

Soluble factors from rat basophilic leukemia (RBL-2H3) cells stimulated cooperatively the neurite outgrowth of PC12 cells.

Culture media from rat basophilic leukemia cells (RBL-2H3) induced the neurite outgrowth of rat pheochromocytoma PC12 cells, a model system for neuronal differentiation. The extension of the neurite outgrowth was dependent on the culture time of RBL-2H3 cells in the DMEM medium. The DMEM medium conditioned by RBL-2H3 cells for 48 h induced neurite outgrowth of PC12 cells significantly. The neurite extension was much higher than that by medium containing 1 ng/ml nerve growth factor (NGF) but was rather lower than that by medium containing 10 or 50 ng/ml NGF. The neurite extension by 50 ng/ml NGF was completely suppressed by excess anti-NGF antibody (1-1.5 microg/ml), while the extension by culture medium conditioned by RBL-2H3 cells for 48 h was not completely suppressed in the presence of the same amount of anti-NGF antibody. The neurite extension by the culture medium of RBL-2H3 cells was also suppressed by anti-interleukin (IL)-6 antibody (1 microg/ml), although IL-6 itself (20 units) could scarcely induce the neurite outgrowth of PC12 cells. This suggests that IL-6 in the culture medium of RBL-2H3 cells could be effective in inducing the neurite extension in cooperation with NGF. In the presence of an excess of both anti-NGF and anti-IL-6 antibodies, the culture medium of RBL-2H3 cells induced the neurite extension of PC12 cells. This suggests that the action of the various factors from RBL-2H3 cells may be synergistic as far as the neurite outgrowth of PC12 cells is concerned.

Animals↗