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Biomedical subjects

M Saito

Publications and source records attributed to M Saito.

At least 37 records · Page 2Linked to original sources
PubMed2006

Overexpression and characterization of an iron storage and DNA-binding Dps protein from Trichodesmium erythraeum.

Although the role of iron in marine productivity has received a great deal of attention, no iron storage protein has been isolated from a marine microorganism previously. We describe an Fe-binding protein belonging to the Dps family (DNA binding protein from starved cells) in the N(2)-fixing marine cyanobacterium Trichodesmium erythraeum. A dps gene encoding a protein with significant levels of identity to members of the Dps family was identified in the genome of T. erythraeum. This gene codes for a putative Dps(T. erythraeurm) protein (Dps(tery)) with 69% primary amino acid sequence similarity to Synechococcus DpsA. We expressed and purified Dps(tery), and we found that Dps(tery), like other Dps proteins, is able to bind Fe and DNA and protect DNA from degradation by DNase. We also found that Dps(tery) binds phosphate, like other ferritin family proteins. Fe K near-edge X-ray absorption of Dps(tery) indicated that it has an iron core that resembles that of horse spleen ferritin.

Amino Acid Sequence↗
PubMed2006

Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive metabolizers and treated with tacrolimus.

OBJECTIVE: Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus. MATERIALS: 24 recipients who were CYP2C19 EMs were studied. METHODS: Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured. RESULTS: Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. CONCLUSIONS: (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

[Suturing left main bronchus in difficult lung resection for repeated and massive hemoptysis].

A 79-year-old man with repeated and massive hemoptysis due to bronchiectasis was admitted to our department for surgery. The patient had undergone left upper lobectomy for pulmonary tuberculosis, and descending aortic replacement for Stanford type B aortic dissection. The patient underwent occlusion of the left main bronchus by suturing through median sternotomy. The reasons we did not choose completion pneumonectomy were advanced age, poor physical condition immediately after hemorrhagic shock, and the difficulty of performing pneumonectomy due to previous surgery and anastomotic aneurysm of descending aorta. The postoperative course was uneventful and the patient left the hospital on the 16th postoperative day. The patient did not develop pneumonia or empyema thereafter, but died suddenly of unknown etiology 1.5 years postoperatively. Lung exclusion by suturing a bronchus is thought to be a useful alternative for repeated and massive hemoptysis without pneumonia in a case of difficult lung resection.

Aged↗
PubMed2006

Angiopoietin-1, 2 and Tie2 expressions in endometrial adenocarcinoma--the Ang2 dominant balance up-regulates tumor angiogenesis in the presence of VEGF.

We investigated Ang1, Ang2 and Tie2 expressions including balance and intratumoral vessels in the role of angiogenesis of endometrial adenocarcinoma. Immunohistochemical staining was performed on 133 patients with endometrial (endometrioid) adenocarcinoma, including 73 with G1, 34 with G2, and 26 with G3. The levels of Ang1, Ang2 and Tie2 expressions were expressed as staining score. Total vessel count (TVC), microvessel count (MVC) and mean vessel diameter (VD) in the CD34-stained tissues were measured in five hot spot areas at x 200 magnification by image cytometry. These results were compared with high and low vascular endothelial growth factor (VEGF) expressions. Ang1, Ang2, Tie2 and CD34 were expressed in the cytoplasm of tumor cells. A significant correlation was found among Ang1, Ang2 and Tie2 expressions. In high VEGF cases, Ang1 expression was correlated negatively with TVC and MVC, but positively with VD, and the Angl < Ang2 group was significantly higher in TVC and MVC and tended to be smaller in VD than the Ang1 > Ang2 group. VD was significantly larger in G3 than in G1. The Ang1 < Ang2 balance may be one of the key factors for angiogenesis of endometrial carcinoma in the presence of high VEGF expression.

Adenocarcinoma↗
PubMed2006

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats.

BACKGROUND: Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied. METHODS: Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg(-1), bolus, followed by a continuous infusion, 0.4mg kg(-1) min(-1) for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters. RESULTS: The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 +/- 302 ng ml(-1) vs 2388 +/- 582 ng ml(-1)). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 +/- 4180 and 29619 +/- 4431 min ng ml(-1), respectively, vs 39802 +/- 6268 min ng ml(-1)). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 +/- 14 and 132 +/- 15 ml min(-1) kg(-1), respectively, vs 92 +/- 14 ml min(-1) kg(-1)). CONCLUSION: Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.

Anesthetics, Local↗
PubMed2005

Mutations in wheat starch synthase II genes and PCR-based selection of a SGP-1 null line.

Wheat (Triticum aestivum L.) starch synthase II, which is also known as starch granule protein 1 (SGP-1), plays a major role in endosperm starch synthesis. The three SGP-1 proteins, SGP-A1, B1 and D1, are produced by three homoeologous SSII genes, wSSII-A, B, and D. Lines carrying null alleles for each SGP-1 protein have previously been identified. In this report, the mutations occurring in each wSSII gene were characterized, and PCR-based DNA markers capable of detecting the mutations were developed. In the null wSSII-A allele, a 289 bp deletion accompanied by 8 bp of filler DNA was present near the initiation codon. A 175 bp insertion occurred in exon 8 of the null wSSII-B allele. The insertion represented a recently discovered miniature inverted-repeat transposable element (MITE) named Hikkoshi that was first found in a wheat waxy gene. A 63 bp deletion was found at the region surrounding the junction of the fifth exon and intron of the null wSSII-D allele. Based on this information, we designed primer sets to enable us to conduct allele-specific amplifications for each locus. The applicability of these primer sets for breeding programs was demonstrated by reconstructing a line lacking all three SGP-1 proteins using marker-assisted selection. These markers will also be useful in breeding programs aimed at obtaining partial mutants missing one or two SGP-1 proteins.

Alleles↗
PubMed2005

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity.

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.

Adiponectin↗
PubMed2005

Proinsulin C-peptide activates vagus efferent output in rats.

The aim of this study was to examine the effect of proinsulin C-peptide on the autonomic nervous systems in rats. Intravenous administration of C-peptide gradually increased electrophysiological activity of the vagus nerves into the stomach and pancreas for at least 90 min. It also slightly increased gastric acid secretion that was suppressed by the treatment with atropine. Intraperitoneal injection of C-peptide did not affect the basal and stress-induced norepinephrine (NE) turnover rate, a biochemical index of sympathetic nerve activity. These results indicate that C-peptide increases parasympathetic nerve activity without affecting sympathetic nerve activity. This could explain, at least in part, the ameliorating effects of C-peptide on impaired cardiac autonomic nerve functions in patients with type 1 diabetes.

Animals↗
PubMed2005

A candidate autonomous version of the wheat MITE Hikkoshi is present in the rice genome.

A miniature inverted-repeat transposable element (MITE), designated as Hikkoshi, was previously identified in the null Wx-A1 allele of Turkish bread wheat lines. This MITE is 165 bp in size and has 12-bp terminal inverted repeats (TIRs) flanked by 8-bp target site duplications (TSDs). Southern and PCR analyses demonstrated the presence of multiple copies of Hikkoshi in the wheat genome. Database searches indicated that Hikkoshi MITEs are also present in barley, rice and maize. A 3.4-kb element that has Hikkoshi-like TIRs flanked by 8-bp TSDs has now been identified in the rice genome. This element shows high similarity to the 5' subterminal region of the wheat Hikkoshi MITE and contains a transposase (TPase) coding region. The TPase has two conserved domains, ZnF_TTF and hATC, and its amino acid sequence shows a high degree of homology to TPases encoded by Tip100 transposable elements belonging to the hAT superfamily. We designated the 3.4-kb element as OsHikkoshi. Several wheat clones deposited in EST databases showed sequence similarity to the TPase ORF of OsHikkoshi. The sequence information from the TPase of OsHikkoshi will thus be useful in isolating the autonomous element of the Hikkoshi system from wheat.

Alleles↗
PubMed2005

Self-energy correction to momentum-density distribution of positron-electron pairs.

Positron two-dimensional angular correlation of annihilation radiation (2D ACAR), i.e., the 2D projection of the electron momentum densities sampled by positron, in Si is employed to verify the prediction of the density functional theory within the local-density approximation (LDA). Carefully conducted test shows that the LDA introduces small but definite discrepancies to the 2D-ACAR anisotropies. Self-energy calculation using the GW method indicates that density-fluctuation contributes anisotropic momentum-density correction and thus improves the agreement between theory and experiment. These results provide valuable annotations to the arguments concerning the accuracy and validity of the LDA and GW schemes.

Journal Article↗
PubMed2005

Intracranial peripheral primitive neuroectodermal tumor manifesting as abducens nerve palsy.

INTRODUCTION: Peripheral primitive neuroectodermal tumor (PNET) occurring as an extra-axial lesion within the intracranial space and extending to the subarachnoid space is extremely rare. CASE REPORT: An 18-month-old girl presented with an intracranial peripheral PNET manifesting as abducens nerve palsy. Magnetic resonance imaging on admission revealed a lesion affecting the trigeminal and abducens nerves. The tumor was partially removed via the subtemporal approach. Histological examination showed a high-grade, undifferentiated neoplasm of small cell type with positive immunostaining for MIC2. The histological diagnosis was peripheral PNET. OUTCOME: Craniospinal radiotherapy reduced the tumor size, but adjuvant chemotherapy designed for Ewing's sarcomas and PNETs was not effective. She died 1 month after the last chemotherapy, despite whole craniospinal irradiation (total dose 53.2 Gy) and chemotherapy.

Abducens Nerve↗
PubMed2005

High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male Zucker obese rats, but highly toxic to the testis.

We investigated the ability of Garcinia cambogia extract containing (-)-hydroxycitric acid (HCA) to suppress body fat accumulation in developing male Zucker obese (fa/fa) rats. We also examined histopathologically the safety of its high doses. Diets containing different levels of HCA (0, 10, 51, 102 and 154 mmol/kg diet) were fed to 6-week-old rats for 92 or 93 days. Each diet group was pair-fed to the 154 mmol HCA/kg diet group. Epididymal fat accumulation and histopathological changes in tissues were observed. The highest dose of HCA-containing Garcinia cambogia (154 mmol HCA/kg diet) showed significant suppression of epididymal fat accumulation in developing male Zucker obese rats, compared with the other groups. However, the diets containing 102 mmol HCA/kg diet and higher (778 and 1244 mg HCA/kg BW/d, respectively) caused potent testicular atrophy and toxicity, whereas diets containing 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) or less did not. Accordingly, 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) was deemed to be the no observed adverse effect level (NOAEL).

ATP Citrate (pro-S)-Lyase↗
PubMed2005

Diurnal variations of serum leptin in dogs: effects of fasting and re-feeding.

Leptin is a protein synthesized and secreted primarily by adipocytes, and plays a key role in the regulation of energy balance. We have reported that serum leptin is elevated in obese dogs. In the present study, we examined diurnal variations of serum leptin in the dog, with special references to feeding and fasting cycles. Four male beagles were accustomed to feed once a day at 10:00 h, and blood samples were taken every 3 h for 24-36 h. Serum leptin concentration showed clear diurnal variations, being lowest before food intake (2.3+/-0.5 ng/mL) at 09:00 h, and highest (10.5+/-2.4 ng/mL) at 18:00 h. Such diurnal variations disappeared when the dogs were fasted. Serum insulin also showed diurnal variation with higher levels at 12:00-15:00 h. When insulin or glucose was injected in the fasted dogs to mimic the post-prandial insulin rise, serum leptin concentration was significantly increased in 4-8 h, but in both cases to a lesser extents than those after food intake. The results indicate that serum leptin concentrations change diurnally in association with feeding-fasting cycles in the dog, partially due to changes in insulin secretion.

Animals↗
PubMed2005

Infected Charcot spine.

STUDY DESIGN: Case report of an infected Charcot spine following spinal cord injury. OBJECTIVE: To describe this very rare pathological condition and the results of surgical treatment. SETTING: A department of orthopaedic surgery in Japan. METHODS: A 44-year-old man presented with a destructive lesion in the lumbo-sacral spine and a fistula in his back. Anterior bone graft, percutaneous external spinal fixation, and suction/irrigation of the wound were performed. After 4 months, posterior spinal instrumentation surgery was carried out. RESULTS: Primary closure of the fistula and complete bone fusion was achieved after the operation. CONCLUSION: Infection of a Charcot spine, although a rare clinical entity, should be considered as a diagnostic possibility in the spinal cord-injured patients. External spinal fixation is a useful method for the unstable spinal lesion with infection.

Adult↗
PubMed2005

A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan.

BACKGROUND AND OBJECTIVES: Statins (HMG-CoA reductase inhibitors) are one of the most widely prescribed classes of drugs throughout the world, because of their excellent cholesterol-lowering effect and overall safety profile except for rare but fatal rhabdomyolysis arising either directly or indirectly by pharmacokinetic interactions with certain other drugs. As package inserts in pharmaceuticals are the primary source of information for health care providers, we carried out a literature search to examine how crucial information was provided in package inserts of five statins approved in Japan (simvastatin, atorvastatin, fluvastatin, pravastatin and pitavastatin). METHODS: A MEDLINE search from 1996 to June 2004 was carried out to identify studies on clinical pharmacokinetic drug interactions for the five statins. We mainly collected information on area under plasma concentration (AUC) following co-administration of statins with other drugs. The current package inserts used in Japan were obtained from the website of the Pharmaceutical and Medical Device Agency whereas USA package inserts were obtained from the Food and Drug Administration website. RESULTS: The majority of package inserts listed the drugs that interacted with statins with most describing the risk of rhabdomyolysis because of the possibility of increases in blood concentration. However, quantitative information such as change in AUC was provided in only a few cases. Instructions for dosage adjustment are seldom provided in the Japanese package inserts. USA package inserts list almost identical drug interactions as the Japanese package inserts, although they contain more quantitative data, especially for typical cytochrome P450 (CYP) inhibitors. CONCLUSION: All pharmacokinetic drug interactions including relevant quantitative data for potential effectors and details on mechanisms of interaction need to be given in package inserts as soon as the information becomes available, to ensure safe and proper use of the drugs concerned. Including such information in the package insert will be an extremely valuable aid for health care providers.

Area Under Curve↗
PubMed2005

Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring.

OBJECTIVE: In general, drugs are used in accordance with an approved dosage regimen in expectation of an appropriate balance between efficacy and toxicity. However, dose control of drugs with a narrow therapeutic range and marked intersubject variability in pharmacokinetics should be established through individualization of dosing based on therapeutic drug monitoring (TDM). The purpose of this study was to examine differences between the approved dosage regimen and the doses of antiarrhythmic drugs and digoxin used in clinical practice and to examine the influence of TDM on dosing. METHODS: Prescription research of antiarrhythmic drugs was performed at five national hospitals in Japan. Prescriptions for antiarrhythmic drugs (cibenzoline, disopyramide, pirmenol, mexiletine, aprindine, flecainide, pilsicainide, amiodarone and digoxin) were counted for the study period. The mean dose and dose distribution of the drugs were determined in each hospital. Comparisons were made of mean dose obtained in the study with the dosage approved by the authority. In addition, the percentage of patients that received TDM was determined. RESULTS: A difference was seen between the approved dosage and the actual dose. For all drugs except flecainide, the mean dose was smaller than the approved dosage. For all drugs except digoxin, remarkable variations were seen in the dose distribution among the hospitals. Digoxin showed a similar dose distribution among the five hospitals. Overall, the percentage of patients that received TDM was low except for Hospital A. However, TDM of digoxin was relatively common at four of the hospitals. CONCLUSIONS: It is concluded that, with the exception of digoxin, the appropriate dosing regimen for antiarrhythmic drugs is not yet established. The establishment of appropriate dosing regimens for antiarrhythmic drugs requires the more widespread adoption of TDM.

Anti-Arrhythmia Agents↗
PubMed2005

Appropriate dosing regimen of allopurinol in Japanese patients.

OBJECTIVE: Approved dosage regimens for prescription drug products are developed with a view to obtaining a favourable therapeutic index in the overall exposed population. The purpose of this study was to examine differences between the approved dosage regimen and the clinically prescribed doses of allopurinol in major hospitals in Japan. METHODS: The prescribing records for allopurinol were scrutinized at five national hospitals in Japan. Prescription information, including mean dose and the distribution of doses, was extracted for each hospital and the data compared with the dosage recommended in the approved labelling for the product. In addition, therapeutic drug monitoring (TDM) data were examined to evaluate relationships between dose administered, serum concentration of oxypurinol, and clinical efficacy. RESULTS: The mean dose of allopurinol prescribed in the five institutions, 131.7 mg/day, was lower than the approved dosage of 200-300 mg/day. There were no differences in the mean dose between the hospitals, and similar dose distributions were seen among the hospitals. Approximately 60-70% of patients were treated with 100 mg/day and 20-30% with 200 mg/day of allopurinol. The most frequent dosage of allopurinol used in clinical practice was 100 mg/day. In the TDM study, the mean trough serum concentrations of oxypurinol were 9.5+/-3.6 microg/mL (50 mg/day), 13.0+/-6.8 microg/mL (100 mg/day), 19.8+/-12.9 microg/mL (200 mg/day) and 15.7+/-7.3 microg/mL (300 mg/day). The mean values of creatinine clearance were 17.0+/-16.4 mL/min (50 mg/day), 33.5+/-32.8 mL/min (100 mg/day), 57.8+/-33.8 mL/min (200 mg/day) and 94.3+/-35.8 mL/min (300 mg/day, in patients with normal renal function), and showed a downward trend together with a reduction of dosage of allopurinol. Allopurinol was given to 91% (91/100) of patients at a daily dose of 100-200 mg, and the oxypurinol trough serum concentration attained (>4.6 microg/mL) was sufficient to maintain a therapeutic effect in 92.3% (84/91) of these patients. A daily dose of 100-200 mg may be enough to obtain therapeutic serum oxypurinol concentrations in most Japanese patients. CONCLUSIONS: Dose of 100-300 mg/day was an effective and commonly used dosing regimen for allopurinol in Japanese patients. The approved dosage range (200-300 mg/day) may be too high for patients with renal dysfunction, suggesting the recommended dosing regimen for allopurinol should be revised to include the lower doses.

Administration, Oral↗