Biomedical subjects
Publications and source records attributed to T Miyamoto.
A novel triterpene saponin, 3-Osulfate-gypsogenic acid-23-O-beta-D-4-O-sulfate-glucopyranoside (junceoside D), has been isolated from the roots of Arenaria juncea. The structure was characterized mainly by a combination of 2D-NMR techniques, mass spectrometry and chemical methods.
We have investigated the oscillatory behavior of the nematic director for 4-pentyl-4'-cyanobiphenyl (5CB) when it is subjected to a static magnetic field and a sinusoidal electric field. In these experiments the two fields were inclined at about 50 degrees and the frequency of the electric field was varied from several hertz to approximately 1000 Hz. The director orientation was measured using time-resolved deuterium NMR spectroscopy since this has the advantage of being able to determine the state of director alignment in the sample. In fact, for all of the frequencies studied the director is found to remain uniformly aligned. Since the diamagnetic and dielectric anisotropies are both positive the director oscillates in the plane formed by the two fields. These oscillations were observed to continue for many cycles, indicating that the coherence in the director orientation was not lost during this motion. The maximum and minimum angles made by the director with the magnetic field were determined, as a function of frequency, from the NMR spectrum averaged over many thousand cycles of the oscillations. At low frequencies (several hertz) these limiting angles are essentially independent of frequency but as the frequency increases the two angles approach each other and become equal at high frequencies, typically 1000 Hz. Our results are well explained by a hydrodynamic theory in which the sinusoidal time dependence of the electric field is included in the torque-balance equation. This analysis also shows that, for a range of frequencies between the high and low limits, these NMR experiments can give dynamic as well as static information concerning the nematic phase.
OBJECTIVE: Two types of hemodynamic overload, pressure and volume overload, result in morphologically distinct types of cardiac remodeling. We explored the possibility that distinct hemodynamic overload may differentially activate the signal transduction pathway. METHODS: Pressure and volume overload were induced by thoracic aortic banding and carotid-jugular shunt formation in rabbits, respectively. Phosphorylation activities of mitogen-activated protein (MAP) kinase families, Akt, and signal transducer and activator of transcription (STAT) 3 in the left ventricular myocardium were determined by Western blotting using phospho-specific antibodies and were compared between hypertrophied hearts by pressure and volume overload. RESULTS: Pressure and volume overload produced concentric and eccentric cardiac hypertrophy in rabbits, respectively. In pressure-overloaded hearts, extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase, and STAT3 were transiently activated prior to hypertrophic changes. In contrast, activation of ERK1/2, but not p38 MAP kinase and STAT3, was observed only at 12 weeks after shunt surgery. Pressure overload evoked short and biphasic activation of Akt at 15 min and 1 day after aortic banding. In contrast, volume overload induced sustained activation of Akt from 1 day to 1 week. Concordant phosphorylation of downstream targets of Akt, glycogen synthase kinase-3beta (GSK-3beta) and p70 ribosomal S6 kinase (p70(S6K)), in response to Akt activation was observed at 15 min after pressure overload. However in volume-overloaded hearts, phosphorylation of GSK-3beta and p70(S6K) was observed at 6 weeks and at 6 and 12 weeks, respectively, and was not coincident with Akt activation. These findings suggest that phosphorylation of GSK-3beta and p70(S6K) is regulated by an alternative pathway other than Akt in volume-overloaded hearts. CONCLUSION: Pressure and volume overload-induced cardiac hypertrophy is associated with distinct patterns of activation of signal transduction pathways. These data may suggest that stimulus-specific heterogeneity in the signaling pathway plays a role in determining the type of cardiac hypertrophy.
We conducted a prospective, randomized, double-blind, parallel study comparing the antiemetic activity and tolerability of treatment with droperidol (2.5 mg d.i.v. twice daily for 5 days) and placebo, both combined with granisetron (3 mg d.i.v. on the first day) and dexamethasone (16 mg d.i.v. on the first day, 8 mg d.i.v. on days 2, 3, and 4 mg d.i.v. on days 4, 5). A total of 180 lung cancer patients receiving high-dose cisplatin (80 mg/m(2))-containing chemotherapy were enrolled in the study, and 171 of them were capable of being evaluated. The clinical characteristics of the patients in the two treatment arms were well balanced. Complete protection from nausea and vomiting was recorded in the acute phase in 97% of patients who treated with droperidol versus 98% of patients who given the placebo (P=0.920), and in 42% versus 38% in the delayed phase (P=0.615). The multiple logistic regression analysis showed that a history of motion sickness was a significant risk factor for cisplatin-induced delayed emesis (odds ratio [OR]=5.98; 95% CI=2.15 to 16.7, P=0.0006). Droperidol-containing treatment was well tolerated by most patients, however, the incidence of sleepiness in the droperidol group was higher than in the placebo group (69% versus 30%, P<0.0001). In conclusion, our data did not support the hypothesis that addition of droperidol to granisetron and dexamethasone reduces the delayed emesis induced by high-dose cisplatin.
Calcium alginate fibers were prepared by extruding an aqueous sodium alginate solution into an aqueous calcium chloride solution. The fibers were treated with a saturated aqueous calcium hydroxide solution for various periods and their apatite-forming ability was examined in a simulated body fluid (SBF). The calcium alginate fibers were treated with the aqueous calcium hydroxide solution for periods longer than five days formed apatite on their surfaces in SBF, and their apatite-forming ability improved with increasing calcium hydroxide treatment time. The amount of calcium ions released from the fibers also increased with increasing calcium hydroxide treatment time, resulting in acceleration of nucleation and growth of apatite on the fiber surfaces. The resultant apatite-alginate fiber composite is expected to be useful as a flexible bioactive bone-repairing material.
Repeated high-dose chemotherapy (HDC) with stem cell support is advocated for curative treatment of epithelial ovarian cancer patients, requiring large quantities of progenitor cell harvest. Although the switchover to peripheral blood stem cell transplantation has generally made possible the harvest of large quantities of progenitor cells, the minimum threshold is still pertinent for planning the safe conduct of HDC. However, as the minimum threshold for safe peripheral blood stem cell transplantation (PBSCT) is not yet established, this study was designed to clarify the minimum amount of progenitor cells required for prompt recovery of hematopoietic. Retrospective analysis was performed on 52 HDCs administered in 37 ovarian cancer patients. After autologous bone marrow aspiration (10 patients) or peripheral blood stem cell harvest (27 patients), colony-forming unit granulocyte macrophage (CFU-GM) were enumerated prior to cryopreservation. Numbers of CFU-GM were again calculated before reinfusion and the patients were divided into eight groups: 0.13-<0.4, 0.4-<0.7, 0.7-<1.0, 1.0-<3.5, 3.5-<5.0, 5.0-<10.0, 10.0-<20.0 and >20.0 (x 10(5)/kg). The minimum CFU-GM threshold (x 10(5)/kg) was found to be 1.0-<3.5 for platelets and 3.5-<5.0 for white blood cells. Higher infusion doses did not lead to significant benefits in hematopoietic reconstruction. These results indicate that preservation of a minimum of 7-10 x 10(5)/kg CFU-GM is recommended for the safe conduct of tandem HDCs.
Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.
BACKGROUND AND STUDY AIMS: We undertook this retrospective study to evaluate the frequency and prognosis of endoscopic treatment of laterally spreading tumors (LSTs) in the rectum. The recurrence rate for lesions of the lower rectum was compared with that of the upper rectum. PATIENTS AND METHODS: During the period from July 1989 to June 2002, a total of 1237 rectal tumors were detected. LSTs accounted for 6.9 % (85/1237) of all rectal tumors. A total of 224 tumors of the lower rectum were detected among the 1237 rectal tumors. LSTs accounted for 16.1 % (36/224) of all the lower rectal tumors. From 85 LST lesions, 67 were evaluated for their prognosis after endoscopic mucosal resection (EMR). Patients whose LSTs had been resected were followed up by endoscopy at the following frequencies: once 15 (22.4 %); twice (more than 1 year), 20 (29.9 %); three times (more than 3 years), 21(31.3 %); and four times or more (more than 5 years), 11 (16.4 %). RESULTS: A total of 67 patients with endoscopically treated LSTs were followed up by endoscopy. We observed recurrences in two lesions of the upper rectum (2/38, 5.3 %) and five lesions of the lower rectum (5/29, 17.2 %) (P = 0.2364); all seven lesions were resected piecemeal. LSTs whose horizontal margin reached the pectinate line frequently recurred in the lower rectum, at a rate of 80 % (4/5). However, all patients were completely cured by additional endoscopic resections, the greatest number of treatments being four. CONCLUSION: For early detection of recurrence and successful endoscopic cure, further colonoscopic examination within a few months after the first treatment is necessary.
From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive.
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Increased cardiovascular mortality is an unresolved problem in patients with chronic renal failure. Cardiac hypertrophy is observed in the majority of patients with chronic renal failure undergoing haemodialysis. However, the mechanisms, including signal transduction pathways, responsible for cardiac hypertrophy in renal failure remain unknown. We examined the subcellular localization of protein kinase C (PKC) isoforms and phosphorylation activities of 3 mitogen-activated protein (MAP) kinase families in hypertrophied hearts of progressive renal injury rat model by subtotal nephrectomy (SNx). We also examined the effects of a novel angiotensin II type-1 receptor antagonist, CS-866, on the PKC translocation, MAP kinase activity and cardiac hypertrophy in SNx rats. The left ventricle/body weight ratios were significantly larger in SNx rats than in sham rats at 1, 2, and 4 weeks after surgery. The translocation of PKCalpha and epsilon isoforms to membranous fraction was observed in SNx rat hearts at 1, 2, and 4 weeks after surgery. Activation of extracellular signal regulated kinase (ERK) 1/2, but not p38 MAP kinase and c-Jun N-terminal kinase (JNK), was observed at 1 and 2 weeks after surgery. Angiotensin II receptor blockade with CS-866 (1 mg kg-1 day-1) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure. These data suggest that PKC and ERK1/2 are activated by an angiotensin II receptor-mediated pathway and might play an important role in the progression of cardiac hypertrophy in renal failure.
BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.
AIM: To examine the histology of preserved anterior lens capsule in vitrectomised and lensectomised rabbit eyes with and without silicone oil tamponade. METHODS: Forty adult Japanese albino rabbits received two port vitrectomy and lensectomy with or without silicone oil tamponade in one eye under both general and topical anaesthesia. Anterior lens capsule was preserved during operation. After healing intervals residual anterior capsule was histologically observed under light or electron microscopy. RESULTS: Immediately after operation, cuboidal lens epithelial cells were observed on the posterior surface of the preserved anterior capsule. During healing intervals in eyes with or without silicone oil tamponade, regenerated lens structure of Sommerring's ring and fibrous tissue formed in the peripheral and central areas of the residual capsule, respectively. Ultrastructural observation revealed the presence of many vacuoles amid matrix accumulation on the posterior capsular surface, suggesting the deposition of emulsified silicone oil droplets. CONCLUSION: Lens epithelial cells produce regenerated lenticular structure and fibrous tissue on the residual capsule following vitrectomy and lensectomy in rabbits. Silicone oil droplets formed by its emulsification deposit in extracellular matrix accumulated on the posterior surface of the anterior capsule. Emulsified silicone may potentially enhance opacification of residual anterior capsule following pars plana vitrectomy by silicone oil deposition and subsequent activation of lens epithelial cells.
We report what we believe to be the first case of restenosis of the sigmoid sinus after stenting, in a 42-year-old man with an arteriovenous malformation with progressive right hemiparesis secondary to venous hypertension. Angiography revealed severe stenosis of the left sigmoid sinus, which was dilated with a self-expandable stent. Six months after the procedure, however, the sinus was again severely stenosed. Intravascular sonography revealed intimal proliferation in the stented sinus. It was dilated percutaneously, and the venous pressure decreased from 51 to 33 mmHg. On sonography, the intimal tissue decreased in thickness and the diameter of the stent enlarged a little.
A crossover study design was used to investigate the dose-related effects of sevoflurane at end-tidal concentrations of 2.2 to 4.4 per cent on the respiratory rate, blood gases, heart rate, arterial blood pressure and ocular signs of chickens during spontaneous and controlled ventilation. The mean (sd) carbon dioxide partial pressure (PaCO2) increased as the concentration of sevoflurane increased, and was 86 (29) mmHg at an end-tidal concentration of 4.4 per cent during spontaneous ventilation, but was maintained between 29 and 42 mmHg during controlled ventilation. The heart rate increased as the concentration of sevoflurane increased during spontaneous ventilation, but did not change during controlled ventilation. Sevoflurane decreased arterial blood pressure during both spontaneous and controlled ventilation, but a dose-dependent decrease in arterial blood pressure was observed only during controlled ventilation. The mean arterial blood pressure at an end-tidal concentration of 4.4 per cent was significantly higher during spontaneous ventilation than during controlled ventilation. Controlled ventilation prevented the increases in PaCO2 and heart rate that were observed during spontaneous ventilation. The decrease in arterial blood pressure during spontaneous ventilation was less than that during controlled ventilation, possibly owing to the effects of hypercapnia.
Apolipoprotein (apo) E plays a key role in regulating plasma levels of lipoproteins. We investigated the serum apoE concentrations in cows during different lactating stages by ELISA. To confirm the distribution of apoE in lipoprotein fractions, cow plasma was separated by gel filtration, ultracentrifugation and agarose gel electrophoresis. The apoE concentrations during early, mid- and late lactating stages in cows were significantly higher than that during the non-lactating stage. In lactating plasma, apoE eluted in high-density lipoprotein (HDL) fractions separated by gel filtration increased. The portion of this apoE in plasma was 49%. However, when lactating plasma was separated by ultracentrifugation, less then 5% apoE was recovered in the HDL fraction, and more apoE was recovered in the non-lipoprotein fraction (d>1.21 g/ml, 46%). In agarose gel electrophoresis, plasma apoE was found in beta-migrating lipoprotein, but it was not present in alpha-migrating lipoprotein. To purify apoE-containing particles, the HDL fraction separated by gel filtration was pooled and the fraction retained on Heparin-Sepharose chromatography collected. Cholesterol was absent from this fraction. These results suggest that apoE-containing particles, which increased during the lactating stage, were not associated with HDL particles, and that lipid-free forms were included in cow plasma.
Carboxymethylated chitin, gellan gum, and curdlan gels were soaked in a simulated body fluid (SBF) having ion concentrations nearly equal to those of human blood plasma. Some of the gels had been soaked in a saturated Ca(OH)(2) solution, while others had not. The carboxymethylated chitin and gellan gum gels have carboxyl groups, while the curdlan gel has hydroxyl groups. None of the gels formed apatite on their surfaces in the SBF when they had not been subjected to the Ca(OH)(2) treatment, whereas the carboxymethylated chitin and gellan gum gels formed apatite on their surfaces when they had been subjected to the Ca(OH)(2) treatment. The curdlan gel did not form an apatite deposit even after the Ca(OH)(2) treatment. Apatite formation on the carboxymethylated chitin and gellan gum gels was attributed to the catalytic effect of their carboxyl groups for apatite nucleation, and acceleration of apatite nucleation from released Ca(2+) ions. This result provides a guiding principle for obtaining apatite-organic polymer fiber composites. This composite is expected to have an analogous structure to that of natural bone.