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Biomedical subjects

S Matsuoka

Publications and source records attributed to S Matsuoka.

At least 19 recordsLinked to original sources
PubMed2006

Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis.

OBJECTIVES: To study the efficacy and safety of monthly intravenous pulse cyclophosphamide (IVCYC) therapy for progressive interstitial pneumonia in polymyositis/dermatomyositis (PM/DM). METHODS: Seventeen patients with PM/DM/amyopathic DM (mean age 51.4 +/- 10.4, mean follow-up 32 months) who received IVCYC for progressive interstitial pneumonia between August 1993 and October 2002 were studied. Nine patients had failed to respond to previous treatment with high-dose steroid and/or immunosuppressant. Cyclophosphamide (300-800 mg/m2) was given at least six times every 4 weeks. Oral prednisolone (0.5-1 mg/kg/day) was administered for the first 2 weeks and was gradually tapered. Response to treatment was evaluated based on the degree of exertional dyspnea, pulmonary function test and high-resolution computed tomography (HRCT). RESULTS: Eleven of 17 patients showed improvement in their dyspnea; six out of seven patients who had required oxygen treatment before IVCYC no longer did so after IVCYC. Eight of 17 patients had >or=10% improvement of vital capacity (VC)% and 9/17 had >or=10 point reduction in their HRCT score. Twelve patients had exhibited at least one result. Two patients with anti-Jo-1 antibodies showed a flare-up of interstitial pneumonia or myositis. After the IVCYC therapy, mean VC% improved by 15% (from 68 to 83%, P = 0.0034). The extent of abnormal lesions in HRCT was reduced from 24 to 13% (P = 0.0055). There was neither death nor severe toxicities observed. CONCLUSIONS: In this open-label study, IVCYC improved symptoms, pulmonary function tests and HRCT findings in patients with PM/DM. Longitudinal controlled studies are required to further confirm the efficacy of IVCYC.

Adult↗
PubMed2006

Modelling Cl- homeostasis and volume regulation of the cardiac cell.

We aim at introducing a Cl- homeostasis to the cardiac ventricular cell model (Kyoto model), which includes the sarcomere shortening and the mitochondria oxidative phosphorylation. First, we examined mechanisms underlying the cell volume regulation in a simple model consisting of Na+/K+ pump, Na+-K+-2Cl- cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance regulator, volume-regulated Cl- channel and background Na+, K+ and Cl- currents. The high intracellular Cl- concentration of approximately 30 mM was achieved by the balance between the secondary active transport via NKCC1 and passive currents. Simulating responses to Na+/K+ pump inhibition revealed the essential role of Na+/K+ pump in maintaining the cellular osmolarity through creating the negative membrane potential, which extrudes Cl- from a cell, confirming the previous model study in the skeletal muscle. In addition, this model well reproduced the experimental data such as the responses to hypotonic shock in the presence or absence of beta-adrenergic stimulation. Finally, the volume regulation via Cl- homeostasis was successfully incorporated to the Kyoto model. The steady state was well established in the comprehensive cell model in respect to both the intracellular ion concentrations and the shape of the action potential, which are all in the physiological range. The source code of the model, which can reproduce every result, is available from http://www.sim-bio.org/.

Animals↗
PubMed2005

Sivelestat, a specific neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury in conscious rabbits.

The in vivo contribution of neutrophil elastase (NE) in phorbol myristate acetate (PMA)-induced acute lung injury has so far been unclear. This study examined the role of NE in PMA-induced acute lung injury in conscious rabbits, using a specific NE inhibitor, sivelestat sodium hydrate (Sivelestat). A single bolus injection of PMA (40 microg/kg) caused acute lung injury as indicated by an increase in protein concentration and hemorrhage in bronchoalveolar lavage fluid (BALF) 4h after PMA injection. These changes were associated with mild decrease in arterial oxygen pressure and peripheral white blood cell and platelet. When continuously infused starting 1h before and ending 4h post-PMA injection, Sivelestat at 3-30 mg/kg/h that are able to inhibit rabbit NE activity by 60-90%, dose-dependently attenuated both PMA-induced hemorrhagic pneumonitis and the increase in protein concentration in BALF without affecting myeloperoxidase activity in the lung. Histopathological study indicated that sivelestat (30 mg/kg/h) markedly attenuated lung histopathological changes, alveolar hemorrhage and white blood cells migration with evidence of inhibition of NE activity in BALF. These results suggest that NE plays a significant role in PMA-induced acute lung injury and further supports the importance of this enzyme in acute lung injury.

Acute Disease↗
PubMed2004

Contamination by persistent organochlorines in cetaceans incidentally caught along Brazilian coastal waters.

Wide ranges of organochlorine residues were determined in the blubber of franciscana (Pontoporia blainvillei), estuarine dolphin (Sotalia guianensis), Atlantic spotted dolphin (Stenella frontalis), and long-beaked common dolphin (Delphinus capensis) incidentally caught along Brazilian coastal waters. Concentrations of DDTs and PCBs were the highest, followed by CHLs, TCPMOH, dieldrin, TCPMe, heptachlor epoxide, HCB, and HCHs. Unexpectedly, significant pollution of PCBs, DDTs, TCPMe, and TCPMOH were observed in cetaceans from Brazil, implying the occurrence of local sources in the Southern Hemisphere comparable to those in the Northern Hemisphere, probably by high industrialization in Brazil. On the other hand, CHLs, HCB, HCHs, heptachlor epoxide, and dieldrin residue levels in Brazilian dolphins were much lower than those in other species from the Northern Hemisphere. Significant correlations of TCPMe and TCPMOH were found along with PCBs and DDTs, indicating the highly bioaccumulative nature of all these compounds and/or possible similar pollution sources.

Animals↗
PubMed2004

Intracellular Ca(2+) dynamics and sarcomere length in single ventricular myocytes.

The measurements of the sarcomere length in dissociated cardiac ventricular myocytes are discussed using mainly our own experimental data. The striation periodicity of these unloaded cells was found to be that which is to be expected of a myocyte free of the ultrastructural constraints imposed upon it by the normal syncytial matrix of the ventricular wall. The sarcomere length and [Ca(2+)] relationship was consistent as expected from the intact tissue, when it was measured soon after partial rupturing the cell membrane. Miniature fluctuations of individual sarcomere length were demonstrated during rest, which was augmented by the Ca(2+) overload. The [Ca(2+)] could be estimated from the measurements of sarcomere length during the positive staircase of contraction. The usefulness of the optical measurement of sarcomere pattern was indicated.

Animals↗
PubMed2004

Clinical success of Neoral absorption profile.

We investigated the clinical benefits of cyclosporine microemulsion preconcentrate (CyA-MEPC; Neoral) in 16 de novo renal transplant recipients. The dose of CyA-MEPC was managed from AUC(0-4h), with serial target values of AUC(0-4h) at 5000-->4000-->3000-->2000 ng. hr/mL. The frequency of acute rejection episodes was 25%. The decreased renal function reached a low value of 12.5%, and creatinine was stable. Therefore, setting the target AUC(0-4h) value in the early phase at 5000 ng.hr/mL is an effective strategy to prevent acute rejection episodes. The single dose of Neoral given immediately after the renal transplant was 6 mg/kg (making a daily dose of 12 mg/kg). Thereafter, the dose-normalized AUC(0-4h) was set at a constant value to 4 weeks posttransplant. At week 4, the single dose was decreased to 4 mg/kg twice daily (a daily dose of 8 mg/kg). From these studies a daily dose of 12 mg/kg is suggested to be the appropriate amount for the first dose immediately after transplant. The renal biopsy performed at 6 months posttransplant showed neither cyclosporine-induced renal impairments, nor findings of chronic rejection, suggesting that 2000 ng.hr/mL is an appropriate target AUC(0-4h) value in the maintenance phase. These results suggest that it is possible to set the target value of C2 monitoring in the maintenance phase to a value slightly lower than that proposed from other studies.

Adult↗
PubMed2003

Involvement of Ca2+ buffering and Na+/Ca2+ exchange in the positive staircase of contraction in guinea-pig ventricular myocytes.

The mean sarcomere length (SL) of guinea-pig cardiac myocytes was recorded simultaneously with the whole-cell current under voltage-clamp conditions. After blocking both sarcoplasmic reticulum (SR) and L-type Ca(2+) channels with ryanodine, cyclopiazonic acid and nicardipine, strong depolarizing pulses induced only the tonic component of SL shortening through the reverse mode of Na(+)/Ca(2+) exchange (NCX). A positive staircase of SL shortening was observed on applying a train pulses to +60~+100 mV at 2 Hz and trans-membrane Ca(2+) flux was calculated from the time integral of the Na(+)/Ca(2+) exchange current ( I(NCX)). Changes in cytosolic [Ca(2+)] ([Ca(2+)](i)) were determined indirectly using the experimental [Ca(2+)](i)/SL relationship. Cellular Ca(2+) buffering was characterized by a lumped single-component system with a maximum binding capacity of 200 micro M and a dissociation constant of 613 nM. Despite the decrease in driving force, the amplitude of the outwards I(NCX) at +60 mV gradually increased along with the positive staircase. The model simulation suggested that this increase of outwards I(NCX) is caused by a dramatic increase in Ca(2+)-mediated activation of NCX.

Animals↗
PubMed2003

Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death.

OBJECTIVE: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. PATIENTS AND METHODS: Questionnaire responses and ECGs of 29 patients with CPVT were evaluated. Mean (SD) age of onset was 10.3 (6.1) years. RESULTS: The initial CPVT manifestations were syncope (79%), cardiac arrest (7%), and a family history (14%). ECGs showed sinus bradycardia and a normal QTc. Mean heart rate during CPVT was 192 (30) beats/min. Most cases were non-sustained (72%), but 21% were sustained and 7% were associated with ventricular fibrillation. The morphology of CPVT was polymorphic (62%), polymorphic and bidirectional (21%), bidirectional (10%), or polymorphic with ventricular fibrillation (7%). There was 100% inducement of CPVT by exercise, 75% by catecholamine infusion, and none by programmed stimulation. No late potential was recorded. Onset was in the right ventricular outflow tract in more than half the cases. During a follow up of 6.8 (4.9) years, sudden death occurred in 24% of the patients, 7% of whom had anoxic brain damage. Autosomal dominant inheritance was seen in 8% of the patients' families. beta Blockers completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in autosomal dominant cases. CONCLUSIONS: CPVT may arise in certain distinct areas but the prognosis is poor. The onset of CPVT may be an indication for an implanted cardioverter-defibrillator.

Adolescent↗
PubMed2002

Analysis of genetic similarity detected by AFLP and coefficient of parentage among genotypes of sugar cane ( Saccharum spp.).

Despite the economical importance of sugar cane, until the present-date no studies have been carried out to determine the correlation of the molecular-based genetic similarity (GS) and the coefficient of parentage ( f)-estimates generated for cultivars. A comprehensive knowledge of the amount of genetic diversity in parental cultivars, could improve the effectiveness of breeding programmes. In this study, amplified fragment length polymorphism (AFLP) and pedigree data were used to investigate the genetic relationship in a group of 79 cultivars (interspecific hybrids), used as parents in one of the Brazilian breeding programmes, and four species of Saccharum ( Saccharum sinense, Saccharum barberi and two of Saccharum officinarum). The objectives of this study were to assess the level of genetic similarity among the sugar-cane cultivars and to investigate the correlation between the AFLP-based GS and f, based on pedigree information. Twenty one primer combinations were used to obtain the AFLP molecular markers, generating a total of 2,331 bands, of which 1,121 were polymorphic, with a polymorphism rate, on average, of 50% per primer combination. GSs were determined using Jaccard's similarity coefficient, and a final dendrogram was constructed using an unweighted pair-group method using arithmetic average (UPGMA). AFLP-based GS ranged from 0.28 to 0.89, with a mean of 0.47, whereas f ranged from 0 to 0.503, with a mean of 0.057. Cluster analysis using GS divided the genotypes into related subgroups suggesting that there is important genetic relationship among the cultivars. AFLP-based GS and f were significantly correlated ( r= 0.42, P< 0.001), thus the significance of this r value suggests that the AFLP data may help to more-accurately quantify the degree of relationship among sugar-cane cultivars.

Journal Article↗
PubMed2001

Reduced expression and impaired kinase activity of a Chk2 mutant identified in human lung cancer.

The checkpoint kinase Chk2 is phosphorylated and activated in response to DNA damage such as ionizing radiation. Recently, we found a somatic mutation of CHK2 with clear loss of the wild-type allele in human lung cancer. Here we show that the mutant Chk2 exhibits modestly reduced in vitro kinase activity compared with wild type, whereas it is normally phosphorylated and activated after ionizing radiation. Interestingly, this mutant Chk2 protein was found to be less stable than wild type and could be expressed in various cell types only at a significantly reduced (20%) level of wild type. These findings confirm that the DNA damage checkpoint pathway involving CHK2 is indeed inactivated in this fatal adult cancer and also suggest that reduced expression of Chk2 may also be an important inactivating mechanism, contributing to the development of lung cancer.

Animals↗
PubMed2001

Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region-derived stromal cells.

There is controversy as to whether murine definitive hematopoiesis originates from yolk sac (YS) or the intraembryonic region. This study reports the generation of definitive hematopoietic stem cells (HSCs) from both early YS and intraembryonic paraaortic splanchnopleures (P-Sp) on AGM-S3 stromal cells derived from the aorta-gonad-mesonephros (AGM) region at 10.5 days post coitum (dpc). YS and P-Sp cells at 8.5 dpc generated no definitive hematopoiesis-derived colony-forming cells in cocultures with AGM-S3 cells, but spleen colony-forming cells and HSCs capable of reconstituting definitive hematopoiesis in adult mice simultaneously appeared on day 4 of coculture. Precursors for definitive HSCs were present in YS and P-Sp at 8.0 dpc, a time when YS and embryo were not connected by blood vessels. It is proposed that precursors with the potential to generate definitive HSCs appear independently in YS and intraembryonic P-Sp and that the P-Sp or AGM region affords the microenvironment that facilitates generation of definitive hematopoiesis from precursors.

Animals↗
PubMed2001

Development of orally active nonpeptidic inhibitors of human neutrophil elastase.

5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.

Administration, Oral↗
PubMed2001

Evidence for the presence of murine primitive megakaryocytopoiesis in the early yolk sac.

During mouse embryogenesis, primitive erythropoiesis occurs in blood islands of the yolk sac (YS) on the seventh day of gestation. This study demonstrated for the first time the presence of unique primitive megakaryocytic (Mk) progenitors in the early YS, which disappeared by 13.5 days postcoitum (dpc). When 7.5 dpc YS cells were incubated in the presence of stem cell factor (SCF), interleukin (IL)-3, IL-6, erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony-stimulating factor in methylcellulose clonal culture, not only erythroid bursts but also megakaryocyte colonies were observed. The megakaryocytes in the colonies matured to proplatelet stages and produced platelets as early as day 3 of culture, much earlier than those from adult bone marrow, although their ploidy class was lower. These megakaryocytes were stained with acetylcholine esterase, and expressed platelet glycoprotein (GP)Ib beta, GPIIIa, and platelet factor 4 by reverse transcription-polymerase chain reaction analysis. The analysis of hemoglobin types in erythrocytes obtained from hematopoietic multilineage colonies containing the megakaryocytes indicated that the Mk progenitors originated from primitive hematopoiesis. The primitive Mk progenitors formed colonies in the absence of any cytokines in fetal bovine serum (FBS)-containing culture, and SCF, IL-3, EPO, and TPO significantly enhanced the Mk colony formation. In FBS-free culture, however, no colony formation was induced without these cytokines. Because megakaryocytes were detected in 8.5-dpc YS, these unique primitive Mk progenitors may rapidly mature and give rise to platelets to prevent hemorrhage in the simultaneously developing blood vessels until definitive hematopoiesis begins to produce platelets. (Blood. 2001;97:2016-2022)

Animals↗
PubMed2001

CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages.

The CD34 antigen serves as an important marker for primitive hematopoietic cells in therapeutic transplantation of hematopoietic stem cells (HSC) and gene therapy, but it has remained an open question as to whether or not most HSC express CD34. Using a competitive long-term reconstitution assay, the results of this study confirm developmental changes in CD34 expression on murine HSC. In fetuses and neonates, CD34 was expressed on Lin(-)c-Kit(+) long-term repopulating HSC of bone marrow (BM), liver, and spleen. However, CD34 expression on HSC decreased with aging, and in mice older than 10 weeks, HSC were most enriched in the Lin(-)c-Kit(+)CD34(-) marrow cell fraction. A second transplantation was performed from primary recipients who were transplanted with neonatal Lin(-)c-Kit(+) CD34(high) HSC marrow. Although donor-type HSC resided in CD34-expressing cell fraction in BM cells of the first recipients 4 weeks after the first transplantation, the stem cell activity had shifted to Lin(-)c-Kit(+)CD34(-) cells after 16 weeks, indicating that adult Lin(-)c-Kit(+)CD34(-) HSC are the progeny of neonatal CD34-expresssing HSC. Assays for colony-forming cells showed that hematopoietic progenitor cells, unlike HSC, continue to express CD34 throughout murine development. The present findings are important because the clinical application of HSC can be extended, in particular as related to CD34-enriched HSC and umbilical cord blood HSC.

Age Factors↗
PubMed2001

Detectability of pulmonary perfusion defect and influence of breath holding on contrast-enhanced thick-slice 2D and on 3D MR pulmonary perfusion images.

The present study assesses the detectability of perfusion defect and the influence of breathhold on pulmonary magnetic resonance (MR) perfusion imaging using contrast-enhanced thick-slice two-dimensional (2D) fast gradient-echo sequence compared with three-dimensional (3D) fast spoiled gradient-recalled sequence. Dynamic studies were performed in 16 patients. MR perfusion images were interpreted by two independent observers using perfusion scintigraphy as the reference standard. The patients were divided into two groups according to the duration of holding the breath measured during MR imaging. The sensitivity and specificity of 2D MR perfusion imaging in detecting perfusion defects were 93% and 94%, respectively, while those of 3D MR perfusion imaging were 89% and 85%, respectively. The diagnostic accuracy of 2D MR perfusion imaging was significantly higher than that of 3D MR perfusion imaging (P < 0.05) among those who could not hold their breath. Therefore, 2D MR perfusion imaging offers promise for evaluating pulmonary perfusion even among patients who cannot hold their breath.

Adult↗