Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 145 records · Page 8Linked to original sources

PubMed2001

Endoscopic subtotal thyroidectomy for patients with Graves' disease.

Endoscopic thyroidectomy performed via the precordial approach leaves no scarring of the neck, and thus provided excellent results from a cosmetic viewpoint. We applied this technique to perform subtotal thyroidectomy in 12 patients with Graves' disease. Three trocars were inserted in the precordial region, and endoscopic surgery was performed with carbon dioxide insufflation. Vessel management and thyroidectomy were carried out using ultrasonic coagulation devices. The mean operative time was 259.8 min, and the mean blood loss was 90.2ml. There were no postoperative complications such as subcutaneous emphysema or hemorrhage, although hypoparathyroidism and recurrent laryngeal nerve paralysis occurred in one patient. Cosmetically esthetic results were achieved in all patients. These findings indicate that this surgical technique represents an effective method of treating Graves' disease that provides excellent cosmetic results.

Adolescent↗

PubMed2001

STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs.

AMP-Activated Protein Kinase Kinases↗

PubMed2001

A new technique: light-induced fluorescence endoscopy in combination with pharmacoendoscopy.

BACKGROUND: Most cancers and adenomas of the GI tract are easily detected by light-induced fluorescence endoscopy (LIFE-GI). However, some tumors are poorly visualized by using this technique. To investigate whether the spraying of noradrenaline on the lesion provides better visualization of the boundaries of neoplasms, the conventional and LIFE-GI endoscopic observations were made before and after spraying of nonadrenaline. METHODS: Seven patients with gastric cancers were studied. After a conventional fiberscopic examination, a LIFE-GI procedure was performed, and then 20 mL of 0.02% noradrenaline solution was sprayed on the lesion. RESULTS: The normal mucosa became paler than the tumor after spraying noradrenaline, thereby clarifying the tumor boundary in the LIFE-GI image. CONCLUSIONS: The combined use of pharmacoendoscopy with LIFE-GI is useful in the detection of gastric malignant tumors because it enhances the boundaries of these lesions.

Adenocarcinoma↗

PubMed2001

A minor E-selectin ligand, CD65, is critical for extravascular infiltration of acute myeloid leukemia cells.

Adhesive ligands on acute myeloid leukemic (AML) blasts may mediate transmigration and extravascular infiltration. In this study, 30 AML samples were examined for expression and density of adhesion antigens. By univariate analysis, four patients with extravascular infiltration showed significantly higher expression of CD2, CD11a, CD11b, CD11c, CD15, CD65, CD86, and HLA-DR as compared with patients without infiltration. These four patients also showed significantly higher density of CD11a, CD11b, CD11c, CD15 and CD65 expression. By multivariate analysis, CD65 expression was the only significant independent risk factor for infiltration, suggesting that this is a critical adhesion molecule for extravascular AML infiltration.

Acute Disease↗

PubMed2001

Crystal structures of substrate free and complex forms of reactivated BphC, an extradiol type ring-cleavage dioxygenase.

BphC derived from Pseudomonas sp. strain KKS102, an extradiol type catecholic dioxygenase, is a non-heam iron-containing enzyme, playing an important role in the degradation of biphenyl/PCB (Poly Chlorinated Biphenyls) in the microbe. Although we had earlier solved the crystal structure of KKS102 BphC, it was the inactive form with Fe(III) in the active site. In order to determine the active form structure, BphC was re-activated by anaerobic incubation with Fe(II) and ascorbate, and crystallized anaerobically. The crystal structures of activated BphC and its substrate complex (E x S complex) were determined at 2.0 A resolution under cryogenic condition. In addition, crystal structures of unactivated BphC in substrate free and complex forms were also re-determined. Comparison of activated and unactivated E x S complexes reveals that the orientation of the bound substrate in the active site is significantly different between the two. The structural comparison of the substrate free and complex forms of activated BphC show certain small conformational shifts around the active site upon substrate binding. As a result of the conformational shifts, His194, which has been suggested as the catalytic base, takes part in a weak hydrogen bond with hydroxyl group of the substrate.

Anaerobiosis↗

PubMed2001

Analysis of anti-rotavirus activity of extract from Stevia rebaudiana.

Anti-human rotavirus (HRV) activity of hot water extracts from Stevia rebaudiana (SE) was examined. SE inhibited the replication of all four serotypes of HRV in vitro. This inhibitory effect of SE was not reduced on the prior exposure of SE to HCl for 30 min at pH 2. Binding assay with radiolabeled purified viruses indicated that the inhibitory mechanism of SE is the blockade of virus binding. The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected MA104 cells. The inhibitory components of SE were found to be heterogeneous anionic polysaccharides with different ion charges. The component analyses suggested that the purified fraction named as Stevian with the highest inhibitory activity consists of the anionic polysaccharide with molecular weight of 9800, and contains Ser and Ala as amino acids. Analyses of sugar residues suggest uronic acid(s) as sugar components. It did not contain amino and neutral sugars and sulfate residues. These findings suggest that SE may bind to 37 kD VP7 and interfere with the binding of VP7 to the cellular receptors by steric hindrance, which results in the blockade of the virus attachment to cells.

Animals↗

PubMed2001

Characterization of the mitochondrial nad7 gene in Physcomitrella patens: Similarity with angiosperm nad7 genes.

The nad7 gene, encoding the subunit 7 of NADH dehydrogenase complex I, is located in the mitochondrial genome in some species of green algae and seed plants, while it is nuclear-encoded in fungi and animals. In a liverwort, the presence of a mitochondrial nad7 pseudogene, and a nuclear nad7 gene has been reported. We have isolated the mitochondrial nad7 gene of the moss Physcomitrella patens. This gene is transcribed as a monocistronic mRNA and contains two group II introns that correspond to the first two of the four introns in the nad7 genes in angiosperms. Results of phylogenetic analysis supported monophyly of the nad7 genes of mosses and tracheophytes. Available data suggest that the nuclear transfer of the nad7 gene occurred only in the liverwort lineage, which diverged extensively from the mosses and tracheophytes with respect to the nad7 gene.

Journal Article↗

PubMed2001

Serum-free coculture system for ex vivo expansion of human cord blood primitive progenitors and SCID mouse-reconstituting cells using human bone marrow primary stromal cells.

OBJECTIVE: In an attempt to maintain and expand human stem cells, many investigators have used xenogeneic, especially murine, stromal cells and fetal calf serum. Because of the possible transmission of infectious diseases, however, the safety of the delivery of grafts expanded in culture using xenogeneic cells and serum has been debated. Using primary human marrow stromal cells, we established a novel serum-free culture system to expand human primitive progenitors and transplantable stem cells. MATERIALS AND METHODS: Cord blood CD34(+) cells were cultured on a monolayer of human primary marrow stromal cells in the presence of thrombopoietin (TPO), flt3/flk2 ligand (FL), and/or stem cell factor (SCF) under serum-free conditions. After 2 or 4 weeks of culture, cells were examined for clonogenic progenitors and severe combined immunodeficient disorder (SCID) mouse-reconstituting cells (SRC). RESULTS: In the presence of TPO, FL, and SCF, marrow stromal cells supported more than a 100- and 1,000-fold expansion of CD34(+) cells and colony-forming units in culture after 2 and 4 weeks of incubation, respectively. In addition, cobblestone area-forming cells were expanded more than 18- and 60-fold after 2 and 4 weeks of culture, respectively. Furthermore, SRC assay demonstrated augmented engraftment by cultured cells. CONCLUSION: This ex vivo expansion system should prove valuable in clinical settings in which stromal cells are available from recipients or stem cell donors.

Acute Disease↗

PubMed2001

On-site diagnosis of H. pylori infection by urine.

We have recently developed an on-site diagnostic kit for H. pylori infection using urine (utilizing immunochromatographic method employing a nitrocellulose membrane coated by extracted H. pylori antigen). Accordingly, we investigated its usefulness in 155 consecutive dyspeptic patients using the 13C urea breath test as a gold standard and further compared its performance with two commercially available rapid diagnostic kits that use whole blood (Helisal Rapid Blood, and ImmunoCard H. pylori). As the results, the urine based on-site diagnostic kit provided 95.9% sensitivity and 87.9% specificity with 92.9% accuracy, which were comparable or even better than that of both rapid whole blood tests, suggesting its usefulness in screening of H. pylori infection.

Antigens, Bacterial↗

PubMed2001

Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.

To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.

Animals↗

PubMed2001

Was the evolution of plastid genetic machinery discontinuous?

The plastid nucleoid consists of plastid DNA and various, mostly uncharacterized, DNA-binding proteins. The plastid DNA undoubtedly originated from an ancestral cyanobacterial genome, but the origin of the nucleoid proteins appears complex. Initial biochemical analysis of these proteins, as well as comparative genome informatics, suggest that proteins of eukaryotic origin replaced most of the original prokaryotic proteins during the evolution of plastids in the lineage of green plants.

Bacterial Proteins↗

PubMed2001

Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids).

Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production.

Betamethasone↗

PubMed2001

Clarithromycin resistance, but not CYP2C-19 polymorphism, has a major impact on treatment success in 7-day treatment regimen for cure of H. pylori infection: a multiple logistic regression analysis.

Mutations in the gene encoding the CYP2C-19 enzyme for PPI metabolism have been shown to enhance the chance for a cure in a H. pylori-positive patients using a two-week dual-therapy regimen involving omeprazole and amoxicillin. However, the impact of CYP2C-19 genetic polymorphism on eradication rates of a one-week triple-therapy regimen has not been examined. In this cohort study, 156 H. pylori-positive peptic ulcer or NUD patients who presented to our university hospital were recruited. They were treated by one-week omeprazole-amoxicillin-clarithromycin therapy. Host and bacterial predictive factors including H. pylori susceptibility and CYP2C-19 genotyping, as well as cure rate for H. pylori infection, were studied. Cure rate was 85.9% (95% CI: 79-91%) on an intent to treat (ITT) basis. By multiple logistic regression analysis, only clarithromycin resistance had a significant impact on treatment success (odds ratio 28.7: 95% CI: 6-172). CYP2C-19 genetic polymorphism was not associated with a significant change in cure rate. These observations indicate only clarithromycin susceptibility, not CYP2C-19 polymorphism, has a major impact on the treatment success when using a seven-day OAC H. pylori treatment regimen.

Amoxicillin↗

PubMed2001

Prostate-specific antigen, prostate volume and transition zone volume in Japanese patients with histologically proven benign prostatic hyperplasia.

The relationship among age, prostate-specific antigen (PSA) level and prostate volume in Japanese patients with lower urinary tract symptoms (LUTS) and histologically proven benign prostatic hyperplasia (BPH) was examined in order to assess the utility of PSA as a predictor of prostate volume. Two hundred eighteen patients with LUTS were confirmed to have BPH by histological examination for the reason of elevated PSA and/or abnormal digital rectal examination finding. Correlation among PSA, prostate volume and transition zone volume were analyzed in patients classified into age-stratified groups. Prostate volume increased with age. Mean serum PSA increased with age, and the correlation of PSA and prostate volume was determined to be statistically significant in each cohort of age. A correlation coefficient ranged from 0.315 to 0.439. In patients with LUTS and clinical BPH, serum PSA increased with age and was related to prostate volume. PSA might be useful for therapeutic decision making for patients with symptomatic BPH.

Aged↗

PubMed2001

Detection of directed gaze in rhesus monkeys (Macaca mulatta).

To examine the ability of monkeys to detect the direction of attention of other individuals, the authors quantitatively investigated the visual scanning pattern of rhesus monkeys (Macaca mulatta) in response to visually presented images of a human frontal face. The present results demonstrated not only that monkeys predominantly gaze at the eyes as compared with other facial areas in terms of duration and number of fixations, but also that they gaze at the eyes for a longer time period and more frequently when a human face, presented as a stimulus, gazed at them than when the gaze was shifted. These results indicate that rhesus monkeys are sensitive to the directed gaze of humans, suggesting that monkeys pay more attention to the human whose attention is directed to them.

Animals↗

PubMed2001

Stepwise progression of centrosome defects associated with local tumor growth and metastatic process of human pancreatic carcinoma cells transplanted orthotopically into nude mice.

Recent evidence indicates that loss of centrosome integrity may be a major cause of genetic instability underlying various human cancers. The aim of this study was to define the role of centrosome defects during the in vivo tumor progression of pancreatic carcinoma using an orthotopic implantation model. Injection of Suit-2 human pancreatic cancer cells into the pancreata of nude mice reproduced the pattern of local tumor growth and distant metastasis observed in humans. Pancreatic xenografts, peritoneal disseminations, and hepatic metastases were harvested, and tumor cells were examined for centrosomes by immunofluorescence microscopy. Centrosome abnormalities, characterized by increased numbers of centrosomes, were detected in only a small fraction of parental Suit-2 cells in culture, whereas the frequency was markedly increased in cells isolated from the pancreatic xenografts. Abnormal centrosome numbers were found at higher frequencies in metastatic foci than in pancreatic xenografts. A significant positive correlation existed between the fraction of cells with multiple centrosomes and that with multipolar mitotic spindles, suggesting a functional involvement of aberrant centrosomes in spindle disorganization and chromosome missegregation. In addition, the increased frequency of abnormal centrosomes was associated with an enhanced degree of chromosomal instability. These findings suggest a novel model of pancreatic tumor progression whereby a stepwise increase in the magnitude of centrosomal abnormalities confers an increased chance for aberrant mitotic events, thus accelerating genetic instability and causing the tumor to progress to a more advanced stage.

Animals↗

PubMed2001

Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection.

BACKGROUND: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. PATIENTS AND METHODS: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a (13)C urea breath test 1 month after the completion of therapy. RESULTS: The eradication rates of the 5-day RACM regimen and the 7-day RAC regimen were 93% (95% CI: 84--97%) and 81% (95% CI: 71--89%) by intention-to-treat analysis, 94% (95% CI: 86--98%) and 83% (95% CI: 73--91%) by all-patients-treated analysis analysis and 95% (95% CI: 87--98%; P < 0.05) and 82% (95% CI: 72--90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance. CONCLUSIONS: The cure rate of the 5-day RACM regimen was more effective than the 7-day RAC regimen, suggesting that this regimen could be preferable as a first-line therapy for H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection.

BACKGROUND AND AIM: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen. METHODS: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80%. As a result, data on 114 patients (83 males and 31 females; mean age 49.1 +/- 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation. They had either repeated the PPI/AC regimen (n = 34; 5-14 days), or had been administered the PPI/AM regimen (n = 80; 10 days). The cure rates of the two regimens were compared. RESULTS: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35-70) versus 81.3% (95% CI, 71-89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42-79) versus 91.4% (95% CI, 81-97) by per-protocol analysis (P < 0.01). CONCLUSION: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.

2-Pyridinylmethylsulfinylbenzimidazoles↗