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Biomedical subjects

Y Ishii

Publications and source records attributed to Y Ishii.

At least 19 recordsLinked to original sources
PubMed2006

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

Adult↗
PubMed2006

Influence of tilt and decentration of scleral-sutured intraocular lens on ocular higher-order wavefront aberration.

AIM: To investigate the influence of tilt and decentration of scleral-sutured intraocular lenses (IOLs) on ocular higher-order wavefront aberrations. METHODS: In 45 eyes of 36 patients who had undergone scleral suture fixation of posterior chamber IOL, tilt and decentration of IOLs were determined by Scheimpflug videophotography, and higher-order aberration for a 4-mm pupil was measured using the Hartmann-Shack aberrometer. In another 100 eyes of 100 patients after standard cataract surgery with posterior chamber IOL implantation, ocular higher-order aberration was measured. RESULTS: In eyes with scleral-sutured IOL, the mean (SD) tilt angle and decentration were 4.43 degrees (3.02 degrees ) and 0.279 (0.162) mm, respectively. Ocular coma-like aberration in the sutured IOL group was 0.324 (0.170) microm, which was significantly greater than that of the standard cataract surgery group (0.169 (0.061) microm, p<0.001, Student's t test). No significant difference was found in ocular spherical-like aberration between the sutured IOL group (0.142 (0.065) microm) and standard surgery group (0.126 (0.033) microm; p = 0.254). In the sutured IOL group, IOL tilt significantly correlated with ocular coma-like aberration (Pearson's correlation coefficient r = 0.628, p<0.001), but no significant correlation was found between IOL tilt and ocular spherical-like aberration (r = 0.222, p = 0.175). The IOL tilt did not correlate with corneal coma-like (r = 0.289, p = 0.171) and spherical-like (r = 0.150, p = 0.356) aberrations. The IOL decentration did not correlate with any higher-order aberrations. CONCLUSION: In eyes with scleral-sutured posterior chamber IOL, tilting of the lens induces considerable amount of ocular coma-like aberrations.

Aged↗
PubMed2006

The application of a new stapling device for open surgery (Contour Curved Cutter Stapler) in the laparoscopic resection of rectal cancer.

Anastomotic leakage is a serious problem in the laparoscopic resection of rectal cancer. Although stapling devices and techniques for colorectal or coloanal anastomosis have been improved, laparoscopic anastomosis is still technically difficult and the rate of leakage is high. To resolve this problem, a new stapling device (the Contour Curved Cutter Stapler) for open surgery was applied to the laparoscopic resection of rectal cancer. After intracorporeal mobilization and vessel ligation, a 6-cm Pfannenstiel incision was made to insert the device into the peritoneal cavity, and a hand access device was placed on the site. The head of the device was put through a cutoff of the middle finger of a surgical glove, after which the wrist of the glove was attached to the hand access device. To prevent leakage of CO2 gas through the gap between the shaft and the glove, the shaft covered by the glove was tied, and the gap was filled with bone wax. After re-creation of the pneumoperitoneum, the rectum was transected with the stapling device, and the anastomosis was accomplished by the double stapling technique. This technique enabled a reliable transection of the rectum because of the easy handling of the device and the wide laparoscopic view of the lower rectum in the deep pelvis.

Equipment Design↗
PubMed2006

High concentrations of D-amino acids in human gastric juice.

The concentrations of free D- and L-amino acids were determined in the gastric juice from four groups: patients suffering from early gastric carcinoma with or without Helicobacter pylori infection, and patients without carcinoma but with peptic ulcers, duodenal ulcers or chronic gastritis with or without H. pylori infection. H. pylori is a bacterium associated with gastric inflammation and peptic ulcers and is a risk factor for stomach cancer. The highest D-amino acid ratios (free D-amino acid concentration to the total corresponding free D- and L-amino acid concentration) were 29%, 26%, 18%, 4% and 1% for proline, alanine, serine, aspartate and glutamate, respectively. The gastric juice levels of L-alanine, L-serine, L-proline, L-glutamate and D-alanine in the samples obtained from subjects bearing early gastric carcinoma and H. pylori were significantly higher than in the samples from the other three groups. Except for D-alanine, there was no correlation between the D-amino acid concentrations and presence of carcinoma or H. pylori.

Adult↗
PubMed2006

Meta-analysis of prophylactic antibiotic use in acute necrotizing pancreatitis.

BACKGROUND: Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis. METHODS: A meta-analysis of randomized controlled trials was carried out. Medline, Web of Science, the Cochrane controlled trials register and international conference proceedings were searched, with a citation review of relevant primary and review articles. RESULTS: Six of 328 studies assessed were included in data extraction. Primary outcome measures were infected necrosis and death. Secondary outcome measures were non-pancreatic infections, surgical intervention and length of hospital stay. Prophylactic antibiotic use was not associated with a statistically significant reduction in infected necrosis (relative risk (RR) 0.77 (95 per cent confidence interval (c.i.) 0.54 to 1.12); P = 0.173), mortality (RR 0.78 (95 per cent c.i. 0.44 to 1.39); P = 0.404), non-pancreatic infections (RR 0.71 (95 per cent c.i. 0.32 to 1.58); P = 0.402) and surgical intervention (RR 0.78 (95 per cent c.i. 0.55 to 1.11); P = 0.167). It was, however, associated with a statistically significant reduction in hospital stay (P = 0.040). CONCLUSION: Prophylactic antibiotics do not prevent infected necrosis or death in acute necrotizing pancreatitis.

Adult↗
PubMed2006

Identification and analysis of MHC class II DRB1 (Patr-DRB1) alleles in chimpanzees.

The MHC-DRB1 gene is known to display the most extensive allelic polymorphisms among MHC class II genes. We attempted the selective identification of chimpanzee (Pan troglodytes) DRB1 (Patr-DRB1) alleles using the polymerase chain reaction (PCR) technique in three steps: first, we performed Patr-DRB1*02 lineage-specific 8-kb PCR for *02 lineage detection in each chimpanzee; second, we performed 620-bp PCR for amplification of full-length exon 2; and finally, we carried out an insert check using the pattern of microsatellite repeat length variability. In the genomic DNA of 23 chimpanzees, nine Patr-DRB1 alleles containing two new alleles were detected. Our approach provides a relatively effective method of identifying Patr-DRB1 alleles in individual chimpanzees and should also contribute to our understanding of the features of MHC molecules in non-human primates.

Alleles↗
PubMed2006

[Use of a balloon occlusion catheter for descending aortic aneurysm after total arch replacement using the elephant trunk technique].

A 74-year-old man who had previously undergone prosthetic graft replacement of the total aortic arch using the elephant trunk technique and of the abdominal aorta was admitted to our hospital for surgical treatment of descending aortic aneurysm. Computed tomography (CT) on admission revealed descending aortic aneurysm of 6.5 cm in diameter, and the previously placed prosthetic graft was detected in the aneurysm. Surgery for the descending aorta was performed under femoro-femoral partial bypass. During the operation, a balloon occlusion catheter introduced through the right brachial artery into the 'elephant trunk' graft was inflated before the aneurysm was opened, then the previously placed prosthetic graft was cross-clamped and the descending aorta was replaced with a new prosthetic graft with usual fashion. The postoperative course was uneventful.

Aged↗
PubMed2005

A subchronic toxicity study of dunaliella carotene in F344 rats.

Dunaliella carotene, extracted from dunaliella alga (Dunaliella bardawil or Dunaliella salina), for use as a food-coloring agent, has beta-carotene as its mainly constituent. As there have been no reports of toxicological evaluation, a 90-day subchronic toxicity study was here performed in F344 rats at dose levels of 0 (control), 0.63%, 1.25%, 2.5% and 5% in powdered basal diet. The average daily intakes of dunaliella carotene were 352, 696, 1420 and 2750 mg/kg/day, respectively, for males, and 370, 748, 1444 and 2879 mg/kg/day for females. No mortality or treatment-related clinical signs were observed throughout the experimental period in any of the groups. Body weight gain was slightly but significantly (p < 0.05) reduced from week 5 to the end of the experiment in 2.5% and 5% males. Increased PLT were observed in 1.25% and 5% males, and 2.5% and 5% females. Significant elevations or tendencies for increase in serum T. Cho and Ca were observed in all treated males and females, with clear dose-dependence in males. Organ weight measurement and histopathological observation revealed no toxicological changes. Based on growth suppression, no-observed-adverse-effect-levels (NOAELs) were estimated to be 1.25% (696 mg/kg/day) for males and 5% (2879 mg/kg/day) for females. As increases in serum Ca were observed in the lowest group in both sexes, a no-observed-effect level (NOEL) could not be determined in this study.

Administration, Oral↗
PubMed2005

Anorexia and weight loss in male rats 24 h following single dose treatment with orexin-1 receptor antagonist SB-334867.

Acute systemic treatment with the selective orexin-1 receptor antagonist SB-334867 (30 mg/kg, i.p.) has been reported not only to inhibit food intake and to accelerate behavioural satiety in rats, but also to produce a significant loss of bodyweight over the 24 h period post-dosing. The present studies were designed to test the hypothesis that the inhibition of weight gain following acute treatment with SB-334867 is due to a persistent anorectic action of the compound. In Experiment 1, the acute effects of SB-334867 (30 mg/kg, i.p.) on food intake and behaviour in a 1 h test with palatable mash were assessed as a function of injection-test interval. Results confirmed that, when administered 30 min prior to testing, SB-334867 significantly suppressed mash intake and accelerated behavioural satiety. More importantly, significant anorexia and behavioural change were also observed when animals were tested 24 h, but not 48 h, post-dosing. As previously reported, all animals treated with the orexin-1 receptor antagonist lost bodyweight over the 24 h period following acute treatment. The generality of these findings was confirmed in Experiment 2, where acute treatment with SB-334867 (30 mg/kg, i.p.) significantly suppressed home cage chow consumption over the 24 h period post-dosing, an effect also accompanied by a significant loss of bodyweight. The results of Experiment 3 showed that, following i.p. administration of 30 mg/kg, SB-334867 has good CNS penetration, reaches peak plasma and brain concentrations at 30 min, and maintains good exposure over 4 h post-dosing. Overall, current data support the hypothesis that a persistent anorectic action contributes to the significant loss of bodyweight observed 24 h following acute dosing with SB-334867. As the compound is virtually undetectable in plasma or brain beyond 8 h post-dosing, and since nothing is known about potentially active metabolites, we consider the possibility that single dose treatment with SB-334867 results in enduring alterations to the orexin-1 receptor and/or downstream signalling pathways.

Activity Cycles↗
PubMed2005

On Myosin II dynamics in the presence of external loads.

We address the controversial hot question concerning the validity of the loose coupling versus the lever-arm theories in the actomyosin dynamics by re-interpreting and extending the phenomenological washboard potential model proposed by some of us in a previous paper. In this new model a Brownian motion harnessing thermal energy is assumed to co-exist with the deterministic swing of the lever-arm, to yield an excellent fit of the set of data obtained by some of us on the sliding of Myosin II heads on immobilized actin filaments under various load conditions. Our theoretical arguments are complemented by accurate numerical simulations, and the robustness of the model is tested via different choices of parameters and potential profiles.

Actins↗
PubMed2005

Effect of a selective OX1R antagonist on food intake and body weight in two strains of rats that differ in susceptibility to dietary-induced obesity.

An orexin-1 receptor antagonist decreases food intake whereas orexin-A selectively induces hyperphagia to a high-fat diet. In the present study, we evaluated the effect of an orexin antagonist in two strains of rats that differ in their sensitivity to becoming obese while eating a high-fat diet. Male Osborne-Mendel (OM) and S5B/Pl (S5B) rats were treated acutely with an orexin-1 receptor antagonist (SB-334867), after adaptation to either a high-fat (56% fat energy) diet or a low-fat (10% fat energy) diet that were equicaloric for protein (24% energy). Ad libitum fed rats were injected intraperitoneally with SB-334867 at doses of 3, 10 or 30 mg/kg, or vehicle at the beginning of the dark cycle, and food intake and body weight were measured. Hypothalamic prepro-orexin and orexin-1 receptor mRNA expression were analyzed in OM and S5B rats fed at a high-fat or low-fat diet for two weeks. SB-334867 significantly decreased food intake in both strains of rats eating the high-fat diet but only in the OM rats eating the low fat diet. The effect was greatest at 12 and 24 h. Body weight was also reduced in OM rats 1d after injection of SB-334867 but not in the S5B rats. Prepro-orexin and orexin-1 receptor expression levels did not differ between strains or diets. These experiments demonstrate that an orexin antagonist (SB-334867) reduces food intake and has a greater effect in a rat strain that is susceptible to dietary-induced obesity, than in a resistant strain.

Animals↗
PubMed2005

Localization of ubiquitin carboxyl-terminal hydrolase-L1 in cynomolgus monkey placentas.

Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) is a restrictedly expressed enzyme in neural and reproductive tissues, and it is considered to have a significant role in reproduction. In the present study, we investigated the localization of UCH-L1 in placenta of cynomolgus monkeys (Macaca fascicularis). UCH-L1 protein was detected in cytotrophoblasts of chorionic plate and villi, and decidual cells of decidua basalis in cynomolgus monkey placenta, and the amount of UCH-L1 protein in whole placenta increased as pregnancy progressed. These results supported that UCH-L1 is necessary for placental and fetal development in primate placenta. This is the first report to demonstrate the presence of UCH-L1 in primate placenta, and the cynomolgus monkey may be a useful model for the study of the functions of the ubiquitin-proteasome system in human pregnancy.

Animals↗
PubMed2005

Association analysis of tissue inhibitor of metalloproteinase2 gene polymorphisms with COPD in Egyptians.

Proteinase/antiproteinase imbalance is recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). A relative increase in the activities of matrix metalloproteinases might be caused by mutations of tissue inhibitor of metalloproteinase2 (TIMP2). Recently, two polymorphisms of the TIMP2 gene, +853 G/A and -418 G/C (+551 and -720 from the translation initiation site), have been shown to be associated with the development of COPD in the Japanese population. In this study, a case-control association analysis for these polymorphisms was conducted in the Egyptian population using 106 COPD patients and 72 healthy controls. The genotype frequency of +853 G/A was significantly different between the patient and the control groups (P = 0.029), although no significant difference was detected in the allele frequency between the two groups. These results suggest that the +853 G/A polymorphism of the TIMP2 gene might be associated with COPD across ethnicities. In contrast, neither the distributions of genotype nor allele frequencies of -418 G/C were significantly different between the two groups, raising the possibility that a combination of different genetic factors contributes to the development of COPD in different ethnic groups.

Case-Control Studies↗
PubMed2005

Loss of peritubular capillaries in the development of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. In this study, we examined the role of peritubular capillary (PTC) injury in the development of CAN. METHODS: We studied renal biopsies (n = 79) obtained from grafts with CAN. PTC injury was examined morphologically by immunohistochemistry for CD34. These findings were correlated with interstitial fibrosis and graft dysfunction. Humoral immunity involved in CAN was studied by C4d staining. RESULTS: The CAN cases in the present study included chronic rejection (CR) (n = 14, 17.8%) and C4d-positive chronic humoral rejection (CHR; n = 6, 42.9% in CR cases). Irrespective of CR, CHR, or other CAN, the development of CAN was characterized by injury to and loss of identifiable PTCs, accompanied with the development of interstitial fibrosis. In CR and CHR cases, the loss of PTCs was prominent and seemed to progress within a relatively short period after transplantation. A decrease in the number of PTCs significantly correlated with the development of interstitial fibrosis (r = -0.75, P < .001) and impairment of graft function (r = -0.69, P < .001). CONCLUSIONS: Irrespective of whether CR, CHR, or other factors contribute to CAN, the processes involved in its development appear similar and are characterized by progressive injury and loss of PTCs, with the development of renal scarring. Immunohistochemistry for CD34 in human renal biopsies is a useful method for the detection of microvascular injury.

Antibody Formation↗
PubMed2005

Antigenicity of sulfanilamide and its metabolites using fluorescent-labelled compounds.

In order to clarify the onset mechanisms of drug-induced allergies, three fluorescent-labelled compounds were synthesized by subjecting sulfanilamide (SA), a base compound for sulfonamides, and its active metabolites, i.e. sulfanilamide hydroxylamine and sulfanilamide nitroso, to dansylation using dansylchloride. In other words, 5-dimethylamino-N-(4-aminobenzyl)-naphthalenesulfonamide (DNS-4ABA), 5-dimethylamino-N-(4-hydroxylaminobenzyl)-1-naphthalenesulfonamide (DNS-4HABA) and 5-dimethylamino-N-(4-nitrosobenzyl)-1-naphthalenesulfonamide (DNS-4NSBA) were synthesized as model haptens. When analysed by HPLC, a conjugate of DNS-4HABA and glutathione (GSH) with nucleophilic amino acids had two peaks (P-1 and P-2). FAB-MS and 1H-NMR revealed that the DNS-4HABA-GSH conjugate consisted of sulphinamide and semimercaptal. The reactivity of GSH to DNS-4ABA, DNS-4HABA and DNS-4NSBA was quantified by HPLC using an oxidization system (horseradish peroxidase/H2O2). The results show that production of DNS-4NSBA-GSH-conjugate was four to eight times higher than that of DNS-4HABA-GSH conjugate, but that DNS-4ABA did not bind with GSH. Skin reactions were assessed using guinea pigs, and strong delayed erythema was seen with DNS-4NSBA, which bound most strongly with GSH, whereas weak delayed erythema was seen with DNS-4ABA, which did not bind with GSH. This suggests a correlation between GSH conjugate production and skin reactions. DNS-4HABA enzymatically bound with proteins in rat and guinea pig liver cytosol and microsomal fractions. The proteins that bound to DNS-4HABA were purified by HPLC and then subjected to N-terminal amino acid analysis. Ubiquitin (10 kDa) and fatty acid binding protein (30 kDa) were detected in the rat liver cytosol fraction; retinol-dehydrogenase (35 kDa) in the rat microsomal fraction; and glutathione-S-transferase B (mmu) (25 kDa) in the guinea pig liver cytosol fraction. When DNS-4HABA or DNS-4NSBA binds to proteins that play important roles in the body, unexpected adverse reactions may occur. Furthermore, by utilizing our technique using model compounds, it may be possible to identify the carrier proteins of various compounds, including pharmaceutical agents.

Animals↗