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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 37 records · Page 2Linked to original sources

Pharmacological study of BRS, a new bicarbonated Ringer's solution, in haemorrhagic shock dogs.

BACKGROUND AND OBJECTIVES: Sodium bicarbonate is the most physiological alkalinizing agent. The effect of a new bicarbonated Ringer's solution (BRS) containing Mg2+, on metabolic acidosis and serum magnesium abnormality were evaluated and compared with those of acetated Ringer's (ARS), lactated Ringer's (LRS) and Ringer's (RS) solutions in an experimental haemorrhagic shock model with dogs. METHODS: Animals were randomly divided into six groups (n = 6 in each group), a sham-operated group, an operated group without infusion, and 4 operated groups with infusion (BRS, ARS, LRS and RS groups). Each RS was intravenously administered at 60 mL kg(-1) h(-1) for 1.5 h. Arterial blood gases, plasma electrolytes and cardiovascular parameters were analysed. RESULTS: BRS significantly improved blood base excess values, which were decreased by blood-letting, faster and more markedly than did LRS and RS (BRS--6.3 +/- 0.5 mEq L(-1); LRS--9.2 +/- 1.1 mEq L(-1); RS--12.4 +/- 1.0 mEq L(-1) at the end of infusion). The alkalinizing effect of BRS tended to be better than that of ARS but not significantly so. The serum Mg2+ concentration was well-maintained by BRS as compared to other RS (BRS 1.5 +/- 0.0 mgdL(-1); ARS 1.2 +/- 0.0mgdL(-1); LRS 1.1 +/- 0.0mgdL(-1); RS 1.3 +/- 0.1 mgdL(-1), at the end of infusion). CONCLUSIONS: These results suggest that BRS is a suitable perioperative solution for metabolic acidosis and serum electrolyte balance among RS tested.

Acid-Base Equilibrium↗

Quality-of-life assessment in community-dwelling, middle-aged, healthy women in Japan.

OBJECTIVES: To determine the quality of life (QOL) of middle-aged Japanese healthy women during the menopausal transition, to identify the correlation between decreasing quality of life and the severity of menopausal symptoms in those women, and to evaluate the number of women who sought treatment/health-care support and their expectations for health-care services. METHODS: This was a community-based study, performed in collaboration with the Munakata Women's Midlife Health Project. The participants attended an annual medical check-up and cancer screenings, and led an everyday life without receiving medical treatment. Their quality of life was assessed with the World Health Organization QOL assessment (WHOQOL) and the severity of menopausal symptoms was assessed with the Kupperman index. Their expectations for health-care services were determined with an open-ended questionnaire. RESULTS: The mean scores of the Kupperman index in the peri- and postmenopausal states were significantly higher than that in the premenopausal states, whereas there was no significant difference of quality of life scored by the WHOQOL in the three groups. In spite of recruiting healthy middle-aged women, 24.4% of the perimenopausal and 26.6% of the postmenopausal women suffered from moderate or severe menopausal symptoms. The decreasing level of quality of life was correlated with the severity of the menopausal symptoms in the peri- and postmenopausal women. The participants did not receive medical support except in two cases, but 83.0% of them wished to participate in a seminar concerning menopause. Several of them sought treatment, health-care support and advice on how to maintain their health during and after the menopausal transition. CONCLUSIONS: Nearly one-quarter of Japanese community-dwelling, healthy women in the peri- and postmenopausal states suffered from menopausal symptoms, which decreased their quality of life in everyday life.

Body Mass Index↗

Possible link between glycolysis and apoptosis induced by sodium fluoride.

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

Apoptosis↗

Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension.

OBJECTIVES: To examine whether autoantibodies against bone morphogenetic protein receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated with pulmonary arterial hypertension (PAH) in patients with mixed connective tissue disease (MCTD). METHODS: We studied sera from 37 MCTD patients with or without PAH, six patients with idiopathic PAH, and 30 healthy controls. Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using immunoprecipitation of recombinant antigens generated by in vitro transcription/translation and indirect immunofluorescence of cultured cells that were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies were further examined by immunoprecipitation and immunoblotting using a recombinant fragment of the extracellular domain of BMPR-II. RESULTS: Serum anti-BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients irrespective of the presence or absence of PAH, or in patients with idiopathic PAH. CONCLUSIONS: Our finding does not support the hypothesis that autoantibody-mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the development of PAH in patients with connective tissue diseases.

Activin Receptors, Type I↗

Ultrafast manipulation of antiferromagnetism of NiO.

Photoexcitation of antiferromagnetic NiO leads to ultrafast reorientation of Ni2+ spins due to change of the magnetic anisotropy. Recovery of the magnetic ground state occurs as coherent oscillation of the antiferromagnetic order parameter between hard- and easy-axis states manifesting itself as quantum beating. The coherence time is approximately 1 ns with the beating frequency being determined by the anisotropy energy.

Journal Article↗

Transluminal color-coded three-dimensional magnetic resonance angiography for visualization of signal intensity distribution pattern within an unruptured cerebral aneurysm: preliminarily assessment with anterior communicating artery aneurysms.

The natural history of unruptured cerebral aneurysm is not known; also unknown is the potential growth and rupture in any individual aneurysm. The authors have developed transluminal color-coded three-dimensional magnetic resonance angiography (MRA) obtained by a time-of-flight sequence to investigate the interaction between the intra-aneurysmal signal intensity distribution patterns and configuration of unruptured cerebral aneurysms. Transluminal color-coded images were reconstructed from volume data of source magnetic resonance angiography by using a parallel volume-rendering algorithm with transluminal imaging technique. By selecting a numerical threshold range from a signal intensity opacity chart of the three-dimensional volume-rendering dataset several areas of signal intensity were depicted, assigned different colors, and visualized transparently through the walls of parent arteries and an aneurysm. Patterns of signal intensity distribution were analyzed with three operated cases of an unruptured anterior communicating artery aneurysm and compared with the actual configurations observed at microneurosurgery. A little difference in marginal features of an aneurysm was observed; however, transluminal color-coded images visualized the complex signal intensity distribution within an aneurysm in conjunction with aneurysmal geometry. Transluminal color-coded three-dimensional magnetic resonance angiography can thus provide numerical analysis of the interaction between spatial signal intensity distribution patterns and aneurysmal configurations and may offer an alternative and practical method to investigate the patient-specific natural history of individual unruptured cerebral aneurysms.

Aged↗

Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer.

To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with gemcitabine, and to observe their antitumour activity, we conducted a combination phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8, every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC who received no prior chemotherapy or one previous chemotherapy regimen were enrolled. The most frequent toxicities were neutropenia and thrombocytopenia; nonhaematological toxicities were generally mild. Three out of six patients experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine, which was regarded as the MTD. There were three partial responses, for an overall response rate of 16.7%. The median survival time and 1-year survival rate were 9.1 months and 34.1%, respectively. This combination is well tolerated and active for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and further evaluation in prospective randomised trials with cisplatin- or carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.

Adult↗

Aberrant dynamics of histone deacetylation at the thyrotropin-releasing hormone gene in resistance to thyroid hormone.

Histone acetylation status influences transcriptional activity, and the mechanism of negative gene regulation by thyroid hormone remains unclear, although its impairment by a mutant thyroid hormone receptor (TR) is critical for resistance to thyroid hormone (RTH). We found a novel RTH mutant, F455S, that exhibited impaired repression of the TRH gene and had a strong dominant-negative effect on the gene. F455S strongly interacted with nuclear receptor corepressor (NCoR) and was hard to dissociate from it. To analyze the dynamics of histone acetylation status in vivo, we established cell lines stably expressing the TRH promoter and wild-type or F455S TR. Treatment with a histone deacetylase (HDAC) inhibitor completely abolished the repression of the gene by T3. The histones H3 and H4 at the TRH promoter were acetylated, and addition of T3 caused recruitment of HDACs 2 and 3 within 15 min, resulting in a transient deacetylation of the histone tails. TR and NCoR were located on the promoter, and T3 caused NCoR dissociation and steroid receptor coactivator-1 recruitment. In the presence of F455S, the histones were hyperacetylated, and HDAC recruitment and histone deacetylation were significantly impaired. This is the first report demonstrating the direct involvement of aberrant dynamics of chromatin modification in RTH.

Acetylation↗

Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma.

Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. (In this study, working with a bleomycin(BLM)-induced scleroderma model mice, we performed two transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-beta1 mRNA and the production of TGF-beta1 on macrophage-like cells that infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.

Animals↗

In vivo transfection of a cis element 'decoy' against signal transducers and activators of transcription 6 (STAT6)-binding site ameliorates IgE-mediated late-phase reaction in an atopic dermatitis mouse model.

Signal transducers and activators of transcription 6 (STAT6) play a crucial role in the transactivation of IL-4 and IL-13, which might be involved in the pathogenesis of atopic dermatitis (AD). We herein reported that the IgE-mediated late-phase reaction significantly decreased in STAT6-deficient (STAT6(-/-)) mice in AD model mice induced by intravenous injection of monoclonal anti-dinitrophenyl (DNP)-IgE antibody and subsequent skin testing with dinitrofluorobenzene. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for STAT6 could be introduced in vivo as decoy cis elements to bind the transcriptional factor and block the gene activation contributing to the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODNs), but not scramble decoy ODN after sensitization by anti-DNP-IgE antibody, had a significant inhibitory effect on not only STAT6 binding to nuclei but also on the late-phase response. A histological analysis revealed that both edema and the infiltration of neutrophils and eosinophils significantly decreased in STAT6 decoy ODN-transfected mice. To examine the mechanism of the in vivo effect of STAT6 decoy ODN, we employed an in vitro mast cells culture system. After IgE receptor engagement, mast cells transfected by STAT6 decoy ODN exhibited normal histamine release, but their cytokine release (TNF-alpha, IL-6) markedly decreased. We herein report the first successful in vivo transfer of STAT6 decoy ODN to reduce the late-phase reaction, thereby providing a new therapeutic strategy for AD.

Animals↗

In vivo transfection of a cis element 'decoy' against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity.

We herein demonstrate that STAT6 plays an important role in the induction of not only acute contact hypersensitivity (CHS), but also chronic CHS in a mouse model using STAT6-deficient (STAT6(-/-)) mice. We, therefore, determine whether synthetic double-stranded DNA with a high affinity for STAT6 can be introduced in vivo as a decoy cis element to bind the transcriptional factor and block the induction of not only acute CHS but also chronic CHS. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), after the induction of 2,4,6-trinitrochlorobenzene or other haptens had a significant inhibitory effect on the induction of both acute CHS and chronic CHS. We thus examined the mechanism of the in vivo effect of the transfection of STAT6 decoy ODN in both acute and chronic CHS. In the histological analysis, the infiltration of eosinophils and degranulated mast cells, and the production of IL-4, IL-6 and eotaxin, but not IFN-gamma in the extracts from challenged skin significantly decreased by the transfection of STAT6 decoy ODN. We herein report the first successful in vivo transfer of STAT6 decoy ODN to inhibit acute and chronic CHS, thus providing a new therapeutic strategy not only for the treatment of CHS but also for atopic dermatitis.

Acute Disease↗

Cerebellar focal granulomatous meningoencephalitis in a dog: clinical findings and MR imaging.

The authors encountered a dachshund dog, presenting vestibular disorder. On magnetic resonance (MR) imaging, a mass showing isointensity on the T1- and T2-weighted images and enhanced by contrast medium, was observed in the right cerebellum. In addition, the periphery of the mass showed isointensity on the T1-weighted image and hyperintensity on the T2-weighted image, suggesting sever oedema. Although the dog underwent surgery, it died. The mass was diagnosed pathologically as a granulomatous meningoencephalitis.

Animals↗

Mechanism of improvement in exercise capacity after the maze procedure combined with mitral valve surgery.

OBJECTIVE: To clarify the mechanism of improvement in exercise capacity after the maze procedure. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 26 patients (mean (SD) age 57 (9) years) with atrial fibrillation (AF) and mitral valve disease were studied with echocardiography and cardiopulmonary exercise testing before and after the maze procedure combined with mitral valve surgery. Of these, eight had persistent AF and 18 had restored sinus rhythm (SR) by the surgery. Six patients (mean (SD) age 59 (12) years) with AF undergoing mitral valve surgery without the maze procedure who had cardiopulmonary exercise testing before and after the surgery formed the control group. MAIN OUTCOME MEASURES: Echocardiographic parameters of atrial function were measured from transmitral flow recordings. Peak oxygen uptake (VO2) and the slope of the relation between VO2 and workload (ratio of DeltaVO2 to Delta work) were determined as indices of exercise capacity. RESULTS: The degree of improvements in peak VO2 and the ratio of DeltaVO2 to Delta work after the mitral valve surgery was comparable between the maze and control group. It was also comparable between patients with and those without successfully restored SR after the maze procedure. The degree of the increase in peak VO2 correlated with the change in left atrial diameter (r = -0.40, p = 0.047) but atrial contraction did not correlate with the increase. CONCLUSIONS: Improvement in exercise capacity may not be caused by restored SR and atrial contraction but may at least partly relate to the reduction of left atrial size and improvement of haemodynamic variables by the surgery.

Adult↗

Region-specific chromatin decondensation and micronucleus formation induced by 5-azacytidine in human TIG-7 cells.

A human diploid lung fibroblast cell strain, TIG-7, has a heteromorphic chromosome 15 with an extra short arm carrying a homogeneously staining region (15p+hsr). We demonstrated previously that the 15p+hsr consists of an inactive and G+C-rich rDNA cluster characterized by fluorescence in situ hybridization (FISH) and various chromosome banding techniques. Thus, it was suggested that the region could contain highly methylated DNA. To observe methylation status on the target region directly under the microscope, we used a demethylating agent, 5-azacytidine (5-azaC), to induce decondensation of the chromatin containing methylated DNA. At 24 h after treatment with 0.5 microM 5-azaC, marked decondensation of the 15p+hsr was observed in almost all of the metaphases. Furthermore, we observed micronuclei, which were equivalent to the rDNA of the 15p+hsr demonstrated by FISH in the same preparation. In contrast, the DNA cross-linking agent mitomycin C (MMC) preferentially induced 15p+hsr-negative micronuclei. These findings indicated that chromatin decondensation and subsequent DNA strand breakage induced by the demethylating effect of 5-azaC led specifically to 15p+hsr-positive micronuclei.

Azacitidine↗

The proposal of noninvasive quantitative diagnostic method of the atherosclerosis and the clarification of organ correlation of atherosclerosis and oxygen metabolism.

The proposal of noninvasive diagnostic method of mechanical degradation of vascular wall is clinically useful and it will be correlated with noninvasive diagnostic method of atherosclerosis. Supersonic Doppler effect sensor has been used to measure blood flow velocity as a noninvasive measuring method. However, it is remain problem whether the output from the Doppler effect sensor really detects the pure blood flow velocity. Theoretically, when the Doppler effect sensor is set perpendicular to the blood flow direction, that is, perpendicular to the blood vessel, the output will correspond to the expansion velocity of blood vessel wall, because it detect the frequency of Doppler shifted supersonic scattered from vascular wall. Previously, on the basis of this concept, using Doppler effect sensor, we showed this method can really detect the deformation velocity of blood vessel wall and it correlates the degradation of elastic property of blood vessel. Furthermore, using this proposed measuring method, atherosclerosis is found to progress correspondingly with the visco-elastic degradation of vascular wall. In this paper, on the basis of our proposed method, the quantitative noninvasive estimation method of the degradation of vascular wall and the progressive degree of atherosclerosis by unique parameter has been proposed. Using this method, the degradation of vascular wall is correlated to the oxygen metabolic function of blood vessel corresponding to the function of oxygen transportation and progression of atherosclerosis. Furthermore, the organ correlation on the atherosclerosis between lower limb and carotid is investigated by this proposed method.

Algorithms↗

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review.

We describe a patient with systemic lupus erythematosus (SLE) who developed severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of TTP and the patient was rescued by extensive plasma exchange started promptly after the diagnosis. Because manifestations of TTP are similar to those in SLE, it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients. We emphasise here the significance of the early diagnosis of TTP by the observation of fragmented RBC and the intensive therapy, including plasma exchange, for this very severe condition.

Adult↗