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H Saito

Publications and source records attributed to H Saito.

At least 19 recordsLinked to original sources
PubMed2007

Ultra-early MRI showing no abnormality in a fall victim presenting with tetraparesis.

STUDY DESIGN: Case report. SETTING: Department of Neurosurgery, Sapporo Azabu Neurosurgical Hospital and Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. CASE REPORT: A patient presented to us with complete C4 tetraplegia after a 3-m fall. MRI performed 120 min after his fall showed spinal canal stenosis due to disk protrusion at the C3/4 level without spinal cord signal changes on T1- and T2-weighted images. He underwent laminoplasty between C2 and C6. Intraoperative ultrasound, performed 6 h after his fall, disclosed a hyperechoic lesion at the C3/4 level of the cervical cord; postoperative T2-weighted MRI, obtained at 8 h after his fall, showed high intensity at the same level. CONCLUSION: In patients with cerebral infarction, approximately 6 h between the insult and the acquisition of T2-weighted MRI are required to detect signal changes. We postulate that the time course on MRI scans obtained immediately after spinal cord injury is similar in patients with spinal cord injury and cerebral infarction and suggest that the absence of spinal cord abnormalities in the ultra-early post-injury stage is not always predictive of a good prognosis.

Accidental Falls↗
PubMed2006

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Adult↗
PubMed2006

Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.

BACKGROUND: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. OBJECTIVES: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. METHODS: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. RESULTS: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). CONCLUSIONS: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

Aged↗
PubMed2006

Performance of GDx VCC in eyes with peripapillary atrophy: comparison of three circle sizes.

PURPOSE: A scanning laser polarimetry (GDx VCC) equips three different sized measurement circles. In eyes with peripapillary atrophy (PPA), the GDx measurement becomes inaccurate when the circle falls on PPA. The aim of this study was to evaluate performance of the three circles of GDx measurement in eyes with PPA. METHODS: Three different sized circles were compared regarding frequency of PPA, which fell on each circle in 282 open-angle glaucoma (OAG) eyes, reproducibility of GDx parameters in 24 normal and 22 OAG eyes, and ability to detect glaucoma in 50 normal and 50 OAG eyes. RESULTS: PPA was observed in 230 (82%) of 282 OAG eyes. PPA fell on the small circle (default setting), medium, and large circles in 119 (43%), 38 (14%), and 12 (4%) of the 280 OAG eyes. Reproducibility of GDx parameters was not significantly different among three circles in normal eyes (P>0.05), whereas coefficients of reproducibility of TSNIT average (P=0.006) and superior average (P=0.035) were smaller in the smaller circles in OAG eyes. GDx parameters significantly correlated (P<0.001), but were significantly different (P<0.05) between the small and medium circles. The area under receiver operating characteristic curves for dividing OAG from normal eyes using GDx parameters was similar between the small and medium circles. CONCLUSIONS: If the medium circles were used, obstructing influences of PPA on GDx measurement could be avoided more often in Japanese OAG eyes with similar reproducibility and comparable ability to detect glaucoma compared to those with the default small circle.

Adult↗
PubMed2006

Pattern of dietary fiber intake among the Japanese general population.

OBJECTIVES: To evaluate the dietary fiber (DF) intake pattern among the Japanese general population. DESIGN: We performed a dietary survey among the general population in northern Japan to evaluate the intake patterns. DF intake was calculated by substituting the DF content of each food in the Dietary Fiber Table for the intake of each food from this dietary survey. SUBJECTS: Five hundred and seventy-seven subjects participated in the study, 198 men and 379 women. RESULTS: In subjects with higher DF intakes the origins of the DF that were from all food groups, but with the notable exception of rice. The contribution of the seaweed group was of particular interest. From multiple regression analysis, as for food group, seaweeds showed the highest positive correlation with DF intake in both genders, followed by vegetables, pulses, fruits. On the other hand, rice showed the negative correlation with DF intake in both genders. As for life factor, body mass index showed the negative correlation with DF intake in women. CONCLUSION: Seaweed, a typical Japanese food, was most related to the increase in DF intake for the Japanese general population, whereas rice, the Japanese staple, had a small influence on decreased DF intake.

Adult↗
PubMed2006

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice.

Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53(-/-) and p53(-/+) backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and alpha-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53(-/+) mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.

Animals↗
PubMed2006

A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer.

The aim of this study was to evaluate the efficacy and tolerability of gefitinib ('IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7-41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemo-naive Japanese patients with advanced NSCLC.

Adult↗
PubMed2006

PTOV1: a novel testosterone-induced atherogenic gene in human aorta.

There are gender differences in the development of atherosclerosis, possibly owing to differences in sex steroid hormone action and/or metabolism. One of the atherogenic effects of testosterone is thought to be androgen receptor (AR)-mediated vascular smooth muscle cell (VSMC) proliferation. However, the detailed mechanism of this effect, particularly the identity of the genes associated with VSMC proliferation, remains largely unknown. Therefore, we first employed microarray analysis and, subsequently, quantitative RT-PCR to analyse RNA expression in AR-positive human VSMCs treated with testosterone in order to detect testosterone-induced genes associated with cell proliferation. We further examined whether the genes identified were involved in cell proliferation using small interfering RNA (siRNA) transfection. Expression of the gene products was then evaluated in human aorta with various degrees of atherosclerosis in order to evaluate the clinical relevance of the findings. Both microarray and quantitative RT-PCR analyses demonstrated marked induction of the human prostate overexpressed protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently identified as a novel androgen-induced gene involved in prostate tumour cell proliferation. Inhibition of PTOV1 by transfection of its corresponding siRNA suppressed testosterone-induced cell proliferation. In human aorta, PTOV1 immunoreactivity in the nuclei of neointimal VSMCs was abundantly detected in male aorta with mild atherosclerotic changes compared with female aorta or male aorta with severe atherosclerotic changes. These findings indicate that the PTOV1 gene is androgen-responsive in VSMCs and that it may play an important role in androgen-related atherogenesis in the human aorta, particularly early atherosclerosis in the male aorta, through regulating proliferation of neointimal VSMCs.

Androgen Antagonists↗
PubMed2006

Identification of tryptase- and chymase-related gene clusters in human mast cells using microarrays.

Tryptase and chymase are the two major granular proteases present in human mast cell (MC)s. We used oligonucleotide microarray to measure the levels of approximately 22,000 transcripts in cord blood-derived MCs at 4 weeks, 8 weeks, 12 weeks and 18 weeks in culture. Tryptase (TPSB2) was expressed at the highest level among all transcripts and its expression level reached a plateau at 8 weeks. On the other hand, the expression level of chymase (CMAI) doubled every 4-6 weeks. A similar tendency was found at the protein levels with FACS analysis. After filtering the transcripts with MC-specificity, hierarchical clustering analysis identified 494 and 81 transcripts in the same clusters with tryptase and chymase, respectively. MC-specific genes, KIT and HDC were found in the tryptase cluster. In the chymase cluster, a critical suppressor for cell senescence, BMI1 and the several related genes were found, suggesting that chymase expression may be closely related to cell senescence/quiescence events.

Cells, Cultured↗
PubMed2006

Alteration and acquisition of Siglecs during in vitro maturation of CD34+ progenitors into human mast cells.

Using human mast cells (MC) derived by culture of CD34+ peripheral blood precursors, a comprehensive study was performed of expression of 11 known Siglecs. Analysis was initially performed at the mRNA level using gene arrays. Positive results were then validated at the protein level using indirect immunofluorescence and flow cytometry, and for some Siglecs, Western blot analysis was also used. Culture-derived MC expressed mRNA for CD22 (Siglec-2), CD33 (Siglec-3), Siglec-5, Siglec-6, Siglec-8 and Siglec-10. Flow cytometry confirmed surface expression of all these molecules except for CD22 and Siglec-10, where levels were low or undetectable. However, Western blotting was able to detect MC expression of CD22 and Siglec-10, suggesting that these proteins were mostly cytoplasmic. CD34+ precursor cells from peripheral blood constitutively expressed surface CD33, Siglec-5 and Siglec-10. As they matured into MC, their constitutive levels of CD33 changed little, Siglec-5 and Siglec-10 declined, and Siglec-6 and Siglec-8 appeared de novo, all in parallel with accumulation of histamine and other MC markers, such as surface expression of FcepsilonRIalpha, and CD51. Phenotypic analysis of LAD-2 MC yielded a similar pattern of Siglec expression except that CD22 expression was particularly prominent. Finally, immunohistochemistry confirmed expression of these same Siglecs by mature tryptase-positive MC in human lung tissues. These data demonstrate an extensive and previously unappreciated pattern of Siglec expression on human MC. Whether engagement and signaling through these inhibitory Siglecs can impact MC biology will require further investigation.

Antigens, CD34↗
PubMed2006

OmpC and OmpF are required for growth under hyperosmotic stress above pH 8 in Escherichia coli.

AIMS: To investigate the requirement of outer membrane porins for osmotic adaptation at alkaline pH in Escherichia coli. METHODS AND RESULTS: Escherichia coli mutants deficient in ompC, ompF and both genes were constructed and the growth of these mutants was observed at alkaline pH. The growth rate of the mutant deficient in both ompC and ompF was slower than that of the wild type and mutants deficient in one of these genes under hyperosmotic stress at pHs above 8.0. The decreased rate was recovered when a cloned ompC was introduced to the mutant, but the growth recovery with a cloned ompF was partial. Such growth diminution was not observed at pHs below 8.0. CONCLUSION: OmpC and OmpF were shown to participate in hyperosmotic adaptation at alkaline pH in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report to demonstrate that OmpC and OmpF are required for hyperosmotic adaptation at pHs above 8.0, but not below 8.0.

Adaptation, Physiological↗
PubMed2006

Fatal thrombosis of antithrombin-deficient mice is rescued differently in the heart and liver by intercrossing with low tissue factor mice.

BACKGROUND: We previously reported that the targeted disruption of murine antithrombin (AT) gene resulted in embryonic lethality before 16.5 gestational days (gd) because of severe cardiac and hepatic thrombosis. OBJECTIVE AND METHODS: To investigate the influences of lowered tissue factor (TF) activity upon hypercoagulation of AT-/- embryos, we crossed AT+/- with low TF (mTF-/- hTF+) mice to yield homozygous AT-deficient mice with the extremely low TF activity, that is expressed from the inserted human TF mini gene. RESULTS: AT-/- embryos either with 50% TF (AT-/- mTF+/- hTF+) or with low (approximately 1% TF, AT-/- mTF-/- hTF+) were not born, although the survival was prolonged until 18.5 gd. In both genotypes, histological examination showed disseminated thrombosis in hepatic sinusoidal space or in the portal veins, suggesting that the thrombogenesis caused loss of hepatic blood flow. As in original AT-/-, AT-/- mTF+/- hTF+ showed subcutaneous (s.c.) bleeding and also suffered from the myocardial degeneration apparently because of coronary thrombus formation. However, AT-/- mTF-/- hTF+ had no skin hemorrhage and the thrombosis and degeneration were completely abolished in the heart. Myocardium of adult low TF mice had exhibited fibrosis secondary to hemorrhage; however, it was significantly decreased in low TF mice with AT+/-. CONCLUSIONS: Our current model suggests that, in the heart, TF plays an important role in the thrombogenesis and it counterbalances AT-dependent anticoagulation. AT may be a potent anticoagulant during mice development and the activation and subsequent regulation of TF-procoagulant activity take place differently between the liver and the heart. These differences appear to point to local regulatory mechanisms in murine hemostasis.

Animals↗
PubMed2006

In vitro characterization of missense mutations associated with quantitative protein S deficiency.

OBJECTIVE: To elucidate the molecular consequences of hereditary protein S (PS) deficiency, we investigated the in vitro synthesis of the PS missense mutants in COS-1 cells and their activated protein C (APC) cofactor activities. PATIENTS: Four patients with quantitative PS deficiency suffering from venous thrombosis were examined. RESULTS: We identified three distinct novel missense mutations, R275C, P375Q and D455Y, and two previously reported missense mutations, C80Y and R314H. The P375Q and D455Y mutations were found in one patient and observed to be in linkage on the same allele. The R314H mutant showed the lowest level of expression (32.7%), and the C80Y, P375Q + D455Y, and R275C mutants exhibited a moderate impairment of expression, that is, 43.8%, 49.5%, and 72.3% of the wild type, respectively. Furthermore, pulse-chase experiments demonstrated that all mutants showed impaired secretion and longer half-lives in the cells than the wild type PS. In the APC cofactor assays, the C80Y mutant showed no cofactor activity, and the R275C mutant showed reduced activity, 62.3% of the wild type PS, whereas the R314H and P375Q + D455Y mutants exhibited normal cofactor activity. CONCLUSION: These data indicate that the C80Y and R275C mutations affect the secretion and function of the PS molecule, and that the R314H and P375Q + D455Y mutations are responsible for only secretion defects, causing the phenotype of quantitative PS deficiency observed in the patients.

Adult↗
PubMed2006

[Right atrial blood cyst; report of a case].

A 53-year-old female was admitted to our hospital for examination of an abnormal shadow on chest X-ray. Computed tomography (CT) revealed a large mass of 3 cm in diameter in the right atrium. The mass arose from the right atrial septum and was removed with the interatrial septum. Histological specimen showed a blood cyst contained serous effusion.

Cysts↗
PubMed2005

Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice.

BACKGROUND: While tumour necrosis factor alpha (TNF-alpha) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. METHODS: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. RESULTS: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-alpha administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. CONCLUSIONS: Enhancement of the TNF-alpha/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.

Animals↗
PubMed2005

Bioelectronic detector with monoamine oxidase for halitosis monitoring.

Methyl mercaptan (MM) is known as one of the major chemicals of halitosis (bad breath). In this study, a bioelectronic gas sensor (bio-detector) for gaseous MM was developed and was applied to measure halitosis in breath. The bio-detector consisted of a Clark-type dissolved oxygen electrode, a monoamine oxidase type-A (MAO-A) immobilized membrane and a reaction unit that had liquid and gaseous compartments separated by a hydrophobic porous polytetrafluoroethylene (PTFE) diaphragm membrane. The tip of the electrode covered with MAO-A membrane was placed into the liquid compartment as touching to the PTFE diaphragm membrane. In order to amplify the bio-detector output, a substrate regeneration cycle caused by coupling the monooxygenase with l-ascorbic acid as reducing reaction with reagent system, was applied. The results of MM vapor measurements showed the calibration range of the bio-detector for MM vapor was from 0.087 to 11.5 ppm (correlation coefficient: 0.993) and included the human sense of smell level 5 (0.2 ppm). The bio-detector had good selectivity being attributed to enzyme specificity was obtained for several substances (trimethyl amine, ammonia, dimethyl sulfide, etc.). The bio-detector was applied for halitosis measurement. Expired gases in five subjects were sampled every hour and the concentrations of MM in the expired gases were monitored. The output of bio-detector showed behaviour of halitosis level changes in a day such as increasing with passage of time and decreasing after eating.

Biosensing Techniques↗