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Biomedical subjects

Y Yamada

Publications and source records attributed to Y Yamada.

At least 55 records · Page 3Linked to original sources
PubMed2005

No effect of fluvastatin on the bone mineral density of children with minimal change glomerulonephritis and some focal mesangial cell proliferation, other than an ameliorating effect on their proteinuria.

AIM: There are conflicting data regarding the clinical benefit of the effect of HMG-CoA reductase inhibitors (statins) in osteoporosis. We have reported that fluvastatin (a statin) is effective in improving proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria. The aim of the present study was to clarify the effect of fluvastatin on the bone mineral density, bone metabolic markers, proteinuria, and renal function of children with minimal change glomerulonephritis with some focal mesangial cell proliferation whose glomeruli did not stain positive for IgA and on moderate proteinuria. PATIENTS AND METHODS: We conducted a prospective controlled study of 36 children who had recently been diagnosed with normocholesterolemic minimal change glomerulonephritis with some focal mesangial cell proliferation and moderate proteinuria, and in whom strenuous exercise was restricted. The 36 patients were randomly assigned to receive 20 mg of fluvastatin (group 1) or 5 mg/kg of dipyridamole (group 2) for two years. RESULTS: By the end of the trial, there was no difference in BMD between the groups, and there were no changes in the four bone metabolic parameters. However, the urinary protein, hematuria and BUN levels had significantly decreased in group 1 compared to baseline, and the serum total protein and albumin levels and creatinine clearance had significantly increased in group 1 compared to baseline and group 2. CONCLUSIONS: The results of this study suggest that fluvastatin therapy has an antiproteinuric effect and improves renal function in moderately proteinuric patients with mild histological glomerulonephritis, but does not increase BMD.

Acid Phosphatase↗
PubMed2005

[Off-pump coronary artery bypass grafting using graft to coronary shunt for acute coronary syndrome].

We developed graft to coronary shunt during off-pump anastomosis. Proximal anastomosis of saphenous vein graft (SVG) was done formerly, and vinyl chloride tube, 5 cm long and 2 mm in diameter, was inserted into SVG. Another end was inserted into coronary artery, and continuous suture around the tube was performed before removing the tube. This technique is fit to use for the anastomosis between SVG and #3. Because the tube is easily inserted into those parts without injury of intima, and distal right coronary artery needs enough blood supply. After the revascularization of left anterior descending artery and #3, the heart can be displaced to expose circumflex artery. We adopted this technique to 3 patients with acute coronary syndrome (ACS). Though this technique is not adopted for the patients having stenosis on #4, we conclude that SVG to coronary shunt could be a important part of the strategies of off-pump coronary artery bypass grafting (OPCAB) for ACS patients.

Aged↗
PubMed2004

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin.

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR equivalent m(-2), and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C(5 min) and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks.

Aged↗
PubMed2004

Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study.

AIM: To assess safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis for distal ulcerative colitis. METHODS: Granulocyte and monocyte adsorptive apheresis therapy (five aphereses for 5 consecutive weeks) was performed for 30 consecutive patients with active distal ulcerative colitis. Patient compliance, adverse effects and clinical symptoms were regularly assessed. RESULTS: Adverse effects were noted during nine (6%) apheresis sessions in eight patients; slight headache five, transient abdominal pain with tenesmus two, fever (38 degrees C) one and mild liver dysfunction one. None of these adverse effects was serious and all patients could complete five aphereses. Clinical symptoms (stool frequency and consistency, rectal bleeding, tenesmus and mucus in stools) significantly improved after the third apheresis. Clinical remission (normal stool frequency and no rectal bleeding) was achieved in 21 patients (70%) after five aphereses. The median Disease Activity Index score significantly decreased; from 6 [interquartile range (IQR): 4-7] to 2 (IQR: 1-3) (P < 0.0001). CONCLUSION: In the treatment of active distal ulcerative colitis, granulocyte and monocyte adsorptive apheresis is safe and well-tolerated. Granulocyte and monocyte adsorptive apheresis had a beneficial effect on clinical remission and symptoms. However, randomized-controlled trials would be necessary to assess a definite efficacy of granulocyte and monocyte adsorptive apheresis.

Adolescent↗
PubMed2004

Mass-fractal clustering and power-law decay of cluster size in 1-propanol aqueous solution.

Mesoscale structure of 1-propanol aqueous solutions with propanol mole fraction xp ranging from 0.1 to 0.33 has been studied by means of small angle neutron scattering (SANS) and large-scale reverse Monte Carlo (RMC) technique. Analysis of the SANS intensities in terms of a fractal model shows that the fractal dimension df of mesoscale structure of the solution is about 1.8-1.9 for water-rich solution and about 1.5 for propanol-rich solution. Percolation analysis on the RMC results reveals that the water molecules and the propanol molecules cluster, respectively, as a mass fractal, the dimension dM of which is about 2.3-2.5 for both clusters for water-rich solution. Furthermore, the distribution of the cluster size is expressed by a simple power law with an exponent tau of about 1.35-1.5 for the propanol clusters and 1.05-1.2 for the water clusters. These results imply that the current solution is characterized by polydisperse mass fractals. In fact, a theoretical relation for polydisperse system of mass fractals, df = dM(2-tau), holds well in the current solution. The characteristic change in df from 1.8-1.9 to 1.5 described above is attributed to the crossover between the water-rich regime and the propanol-rich regime. Most of the water molecules and the propanol molecules are located on the interface between clusters, and the water molecules form thin layers of about 10 A thick irrespective of 1-propanol content studied.

Journal Article↗
PubMed2004

Chronic ethanol consumption does not affect action of propofol on rat hippocampal acetylcholine release in vivo.

BACKGROUND: The aim of this study was to examine ethanol-consumption-related changes in the effects of propofol on rat hippocampal acetylcholine (ACh) release. METHODS: Male Sprague-Dawley rats received a solution of ethanol (20% v/v) for 24 weeks while controls received tap water. The effects of propofol were examined by in vivo microdialysis, with ACh release from the hippocampal regions determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). RESULTS: Propofol 50 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 50.4 (sem 4.7)% and 38.3 (11.1)%, respectively. Propofol 100 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 67.5 (3.7)% and 55.9 (7.4)%, respectively. The reduction in hippocampal ACh release induced by 50 or 100 mg kg(-1) i.p. propofol was not significantly different between ethanol-treated and control rats. There was no significant difference in the duration of sleep between the two groups. CONCLUSIONS: These results demonstrate that chronic ethanol consumption does not augment the inhibitory actions of propofol on rat hippocampal ACh release. These findings appear to be inconsistent with the notion that chronic ethanol intake enhances the propofol-induced inhibition of the hippocampal cholinergic system and related mental dysfunction.

Acetylcholine↗
PubMed2004

Comparison of the efficacy, toxicity, and pharmacokinetics of a uracil/tegafur (UFT) plus oral leucovorin (LV) regimen between Japanese and American patients with advanced colorectal cancer: joint United States and Japan study of UFT/LV.

PURPOSE: To compare the efficacy, toxicities, and pharmacokinetics of an oral regimen consisting of uracil/tegafur (UFT) and leucovorin (LV) between Japanese patients and patients in the United States with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: Forty-four Japanese patients and 45 patients in the United States were enrolled in concurrent nonrandomized phase II trials. UFT 300 mg/m2/d and leucovorin 75 mg/d were administered orally for 28 days followed by a 7-day rest period. The total daily dose of each drug was divided into three equal doses. Treatment was repeated every 5 weeks until disease progression. Blood samples for the pharmacokinetic study were obtained after the initial dose on day 1 of the first course. RESULTS: The response rate for the Japanese patients and the patients in the United States was 36.4% (95% CI, 22.4% to 52.2%) and 34.1% (95% CI, 20.5% to 49.9%), respectively. The only major toxicity was diarrhea, and other toxicities were mild in both populations. The incidence of grade 3 or higher diarrhea in the Japanese and Americans was 9% and 22%, respectively. Although the area under the curve and maximum concentration of fluorouracil were found to be slightly higher in the Japanese patients than the patients in the United States, and area under the curve-adjusted body surface area appeared to be comparable between the two groups. CONCLUSION: The efficacy and pharmacokinetic parameters of UFT and LV are comparable in Japanese and American patients; however, a difference in toxicity profile, specifically diarrhea, was noted. This oral regimen of UFT and LV is considered to have similar activity against metastatic colorectal cancer and to have acceptable toxicity in patients in both countries.

Administration, Oral↗
PubMed2004

Opposite effects of depressant and convulsant barbiturate stereoisomers on acetylcholine release from the rat hippocampus in vivo.

BACKGROUND: It has been shown that the R(-) isomer of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) induces loss of the righting reflex (LRR), while S(+)-MPPB causes pure excitatory effects, including convulsions, in vivo. METHODS: We studied the effects of the depressant and convulsant MPPB stereoisomers on rat hippocampal acetylcholine (ACh) release in vivo, using a brain microdialysis technique in freely moving animals. RESULTS: R(-)-MPPB 60 and 90 mg x kg(-1) i.p. decreased ACh release from the rat hippocampus by 44.1 (8.2)% and 60.8 (8.2)%, respectively. In the hippocampus, the local application of bicuculline, a gamma-aminobutyric acid (GABA)(A) receptor antagonist, 1 micromol litre(-1) antagonized the inhibitory effects of R(-)-MPPB 90 mg x kg(-1) i.p. In contrast, R(-)-MPPB, S(+)-MPPB 60 and 90 mg x kg(-1) i.p. increased ACh release to 151.8 (6.8)% and 169.6 (11.1)% of the basal release, respectively. CONCLUSIONS: Our results demonstrated that R(-)-MPPB decreased, while S(+)-MPPB increased, rat hippocampal ACh release and that the inhibitory effects of R(-)-MPPB may involve the GABA(A) receptor in vivo. These data imply that changes in hippocampal ACh due to these agents may be related to their central inhibitory and stimulatory actions in vivo.

Acetylcholine↗
PubMed2004

Marked asymmetry of putaminal pathology in an MSA-P patient with Pisa syndrome.

We report on an autopsy case of a 62-year-old Japanese woman with a 2.5-year history of axial dystonia. She presented with a form of axial dystonia reminiscent of Pisa syndrome. The pathophysiological mechanism underlying forms of axial dystonia remains to be elucidated. We report here the histopathological findings of a multiple system atrophy of parkinsonian predominance (MSA-P) patient with Pisa syndrome.

Atrophy↗
PubMed2004

Significantly higher incidence of carotid atherosclerosis found in Japanese type 2 diabetic patients with early nephropathy.

We have tried to evaluate the clinical incidence of carotid atherosclerosis found in Japanese type 2 diabetic patients with early diabetic nephropathy. 123 diabetic patients with micro-albuminuria (group A) were investigated during 2-week hospitalization. As a control group, 50 diabetic patients without nephropathy (group B) were investigated. Carotid arteries were examined by B-mode ultrasonography (7.5 MHz), and peripheral arterial blood flow and pressure was examined at the same time with Doppler ultrasonography by a single examiner. Fasting blood samples and 24-h urine samples were taken to analyze biochemical data and urinary albumin excretion rate. In group A, 77 patients were found to have either carotid plaque lesions or increased thickness of carotid wall. And this was found significantly higher than in the control group B (18 cases, P < 0.01). To clarify the clinical risk factors for carotid atherosclerosis in diabetic patients with early nephropathy, 123 group A patients were divided into two groups with (group C, n = 76) or without carotid atherosclerosis (group D, n = 47) and comparative analysis was carried out. From this study, significantly higher incidence of carotid atherosclerosis was confirmed in the diabetic patients with early nephropathy. And it was suggested that the age, lipid levels, presence of hypertension would be important clinical risk factors for carotid atherosclerosis found in diabetic patients with early nephropathy.

Albuminuria↗
PubMed2004

Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes.

To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan, insulin secretion and insulin sensitivity were compared across the range of glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to the criteria of the World Health Organization (WHO). We examined insulin secretion and insulin sensitivity using fasting blood glucose and insulin levels and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI) composite for insulin sensitivity. Although insulin resistance plays an important role in the development of diabetes in many ethnic populations, the differences in insulin sensitivity between NGT and IGT and between IGT and DM are small in Japanese patients. On the other hand, as glucose intolerance increases, insulin secretion decreases most remarkably both between NGT and IGT and between IGT and DM in Japanese patients. Decreasing insulin secretion and decreasing insulin sensitivity both occur in developing type 2 diabetes in Japanese patients, but decreased basal and early-phase insulin secretion had more pronounced contribution to glucose tolerance than the indices of insulin sensitivity. Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance.

Aging↗
PubMed2004

Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients.

OBJECTIVE: Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. METHODS: First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. RESULTS: In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). CONCLUSION: Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.

Adult↗
PubMed2004

Alcohol consumption, homeostasis model assessment indices and blood pressure in middle-aged healthy men.

A total of 1595 middle-aged healthy men consuming alcohol up to 120 ml per day and 538 without alcohol consumption were recruited from an occupational population, and their insulin resistance (IR) and beta-cell function (BC) were measured using the homeostasis model assessment (HOMA-IR and HOMA-BC), and the associations with alcohol consumption, blood pressure (BP), and serum gamma-glutamyltransferase (GGT) levels were analysed cross-sectionally. Both HOMA-IR and HOMA-BC were decreased with increasing alcohol consumption, but HOMA-BC corresponding to a level of HOMA-IR was 4-10 and 8-20% lower in drinkers consuming less than 60 ml of alcohol per day and those consuming more, respectively, than in nondrinkers, suggesting an altered fasting serum insulin-glucose relationship in alcohol consumers. Although BP was higher and HOMA-IR was lower in alcohol consumers than in nonconsumers, BP was higher at higher HOMA-IR irrespective of alcohol consumption. Elevations of serum GGT were positively associated with BP and HOMA-IR in both alcohol consumers and nonconsumers. Multiple regression analyses in the subjects showed that elevated serum GGT was an independent contributor to HOMA-IR elevations, and both serum GGT and HOMA-IR were significantly related to BP elevations after adjusting for alcohol consumption, age, body mass index, cigarette consumption, and physical activity at leisure. Although cross-sectional observations do not provide evidence of causal association, the results suggest that elevated serum GGT in alcohol consumers relates to elevations of IR and that the elevated insulin resistance relates, at least partly, to BP elevations in alcohol consumers.

Adult↗
PubMed2004

Phylogenetic relationships among medically important yeasts based on sequences of mitochondrial large subunit ribosomal RNA gene.

Sequences of the mitochondrial large subunit ribosomal RNA (mtLsurRNA) gene of medically important yeasts were analysed. Sixteen strains of eight species including two varieties were subjected to sequencing. Sequencing enabled us to recognize the differences between all the species and varieties. Alignment analysis revealed that these sequences consisted of three clusters: the Candida albicans group, the C. glabrata group, and the basidiomycetous group. It is possible, therefore, that the mtLsurRNA gene is one of the targets not only for species identification but also for phylogenetic analysis of closely related yeasts. The dendrogram of each group, obtained from this gene, supports the previous study of yeasts based upon the chromosomal genes.

Base Sequence↗
PubMed2004

Measuring tumor volume with three-dimensional endoscopic ultrasonography: an experimental and clinical study (including video).

BACKGROUND AND STUDY AIMS: The Olympus EU-IP2 three-dimensional endoscopic ultrasound (3D-EUS) imaging system makes it possible to display tumors in three dimensions and estimate their volume. MATERIALS AND METHODS: Experimental and clinical studies of the volume estimation function of the Olympus EU-IP2 system was carried out to evaluate its accuracy and assess the extent of tumor shrinkage caused by fixation, dehydration, and staining. Results. In the experimental studies, compared with the actual volume of a 1000-mm (3) gelatin column, the estimated volume was found to be equivalent to 114 +/- 1.8 % with the 3R probe and 143 +/- 0.8 % with the 2R probe (mean plus or minus standard deviation). The mean estimated volume of tumor models was 127 +/- 8.5 % with the 3R probe and 131 +/- 6.8 % with the 2R probe. Greater distance from the probe was associated with a greater degree of error than the target object's size, angle, or the number of traces of its outline made. In the clinical studies, compared with the histologically determined tumor volume (100 %), the mean estimated tumor volume was 178 +/- 48.2 % in situ, 168 +/- 31.3 % in resected specimens, and 137 +/- 31.5 % after fixation. Fixation, dehydration, and staining were thus associated with tumor shrinkage. CONCLUSIONS: The volume of gastrointestinal lesions can be estimated by 3D-EUS, although it is overestimated in comparison with actual values. 3D-EUS also allows direct comparisons to be made between the tumor volume before surgery and the volume of fixed pathological specimens, so that the rate of tumor shrinkage can be estimated.

Colonic Neoplasms↗
PubMed2004

Hepatitis B virus X protein (HBx)-induced apoptosis in HuH-7 cells: influence of HBV genotype and basal core promoter mutations.

BACKGROUND: Hepatitis B virus (HBV) infection is a serious, world-wide problem. HBV genotype and basal core promoter (BCP) mutations affect the clinical course of HBV-infected patients. BCP mutations also lead to mutations at HBV X protein (HBx) codons 130/131. The functional significance of naturally occurring variants of human HBx remains largely unknown. The purpose of the study was to investigate whether HBV genotypes or double mutations affect HBx-induced apoptosis. METHODS: We constructed genotype A, B, C, and D HBx expression vectors and HBx expression vectors with double mutations at HBx codons 130K and 131V or positions 130M and 131I using site-directed mutagenesis. A transient expression system in HuH-7 cells was established and this model was utilized to address the effect of HBx on cell viability. RESULTS: HBx-transfected cells showed a dose-dependent decrease in cell viability by MTS assay. A subset of cells expressing HBx underwent apoptosis according to terminal transferase enzyme-mediated end labeling of DNA and caspase-3 activity. This study demonstrated that HBx can induce cell death by apoptosis in a dose-dependent manner and that HBV genotypes and double mutations did not affect HBx-induced apoptosis. CONCLUSIONS: HBV genotypes and mutation of two amino acids directly adjacent to the conserved Kunitz domain essential for transcription activating activity of HBx did not change the pro-apoptotic activity of HBx. Further study is needed to determine whether HBV genotypes and double mutations have any effect on the function of HBx.

Apoptosis↗