Biomedical subjects
Publications and source records attributed to Osamu Sato.
A novel single-chain magnet, [MnIII3O(Meppz)3(EtOH)4(OAc)] (1), has been successfully synthesized from a secondary building block [MnIII3O(Meppz)3(EtOH)5Cl] (2) with an S = 1 ground state. SCM 1 exhibits both magnetization relaxation and dielectric relaxation properties.
To clarify whether activity of the ryanodine receptor type 2 (RyR2) is reduced in the sarcoplasmic reticulum (SR) of cardiac muscle, as is the case with the ryanodine receptor type 1 (RyR1), Ca(2+)-dependent [(3)H]ryanodine binding, a biochemical measure of Ca(2+)-induced Ca(2+) release (CICR), was determined using SR vesicle fractions isolated from rabbit and rat cardiac muscles. In the absence of an adenine nucleotide or caffeine, the rat SR showed a complicated Ca(2+) dependence, instead of the well-documented biphasic dependence of the rabbit SR. In the rat SR, [(3)H]ryanodine binding initially increased as [Ca(2+)] increased, with a plateau in the range of 10-100 microM Ca(2+), and thereafter further increased to an apparent peak around 1 mM Ca(2+), followed by a decrease. In the presence of these modulators, this complicated dependence prevailed, irrespective of the source. Addition of 0.3-1 mM Mg(2+) unexpectedly increased the binding two- to threefold and enhanced the affinity for [(3)H]ryanodine at 10-100 microM Ca(2+), resulting in the well-known biphasic dependence. In other words, the partial suppression of RyR2 is relieved by Mg(2+). Ca(2+) could be a substitute for Mg(2+). Mg(2+) also amplifies the responses of RyR2 to inhibitory and stimulatory modulators. This stimulating effect of Mg(2+) on RyR2 is entirely new, and is referred to as the third effect, in addition to the well-known dual inhibitory effects. This effect is critical to describe the role of RyR2 in excitation-contraction coupling of cardiac muscle, in view of the intracellular Mg(2+) concentration.
The synergy between the electrical conductivity within the stacks of Ni(dmit)2 in the newly electrocrystallized [Fe(qsal)2][Ni(dmit)2]3.CH3CN.H2O and the spin conversion of Fe(qsal)2 is evidenced. In addition, the presence of a light-induced excited spin state trapping effect suggests that this complex is a prototypal photoswitchable spin-crossover molecular conductor.
Two chain complexes built with non-carboxylate Mn(III)3O units, [Mn3O(ppz)3(MeOH)3(OAc)]n (1) and [Mn3O(Meppz)3(MeOH)4(OAc)]n (2), were synthesized and characterized. Magnetic studies revealed similar intrachain ferromagnetic interactions in them and field-induced metamagnetic properties in 1.
Fatty acid translocase (FAT)/CD36 is a multi-functional membrane protein participating in uptake of long-chain fatty acids and oxidized low density lipoprotein, playing an important role in lipid homeostasis. We reported the dual promoter structures of the mouse and human FAT/CD36 genes in relation to the tissue-specific expression and regulation by peroxisome proliferator-activated receptors (PPARs) (Sato et.al. J. Biol. Chem. 277, 15703-15711, 2002). However, these structures alone could not explain a large induction of the mRNA by a PPAR ligand in the mouse intestine. To learn more about the tissue-specific transcriptional regulation of the FAT/CD36 gene for lipid homeostasis at the whole body level, we cloned the cDNA for the induced mRNA in the mouse intestine and identified third promoter close to the first common exon of the gene. The human gene also has essentially the same gene organization. RT-PCR and Northern blot analyses showed that the three promoters are differentially used in various mouse tissues and the cultured human cells. The physiological significance of these complex promoter structures was suggested by the differential responsiveness to a peroxisome proliferator-activated receptor ligand and the differences in translational efficiencies or stabilities of the mRNA among the isoforms.
A dinuclear complex, [(CoTPA)2(DHBQ)](PF6)3, has been successfully synthesized that exhibits a valence tautomeric transition with a distinct hysteresis effect (13 K) around room temperature and photoinduced valence tautomerism under low temperature.
The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.
In this paper we showed a new approach for the fabrication of a photonic crystal with a three-dimensional structure. By replicating biomaterials such as the wing of Mopho butterfly with TiO2 nanoparticles using the nanoparticles infiltration method, we can derive photonic crystals with unique structures, which is difficult to fabricate by other approaches. New optical properties are anticipated.
A novel pretreatment method has been developed for determination of toxic metals in plastic materials by their decomposition under supercritical water conditions. Particularly, quantitative analysis of cadmium in polyethylene has been demonstrated using inductively coupled plasma atomic emission spectrometry combined with supercritical water treatment. All the cadmium in a polyethylene sample was obtained as an aqueous solution by the treatment with supercritical water containing 12.4% of hydrogen peroxide at 673 K. Although a complete recovery of the aqueous solution from the reactors has not yet been attained, we verified that the present method was effective and promising for quantitative analysis of trace amounts of hazardous metals in plastic materials.
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A new cyanide-containing building block K[Fe(pcq)(CN)(3)] [1; pcq(-) = 8-(pyridine-2-carboxamido)quinoline anion] containing a low-spin Fe(III) center with three cyanide groups in a meridional arrangement has been successfully designed and synthesized. Three cyanide-bridged trinuclear Fe(III)(2)Mn(II) complexes, [Fe(pcq)(CN)(3)](2)[Mn(CH(3)OH)(2)(H(2)O)(2)].2H(2)O (2), [Fe(pcq)(CN)(3)](2)[Mn(bipy)(2)].CH(3)OH.2H(2)O (3), and [Fe(pcq)(CN)(3)](2)[Mn(phen)(2)].CH(3)OH.2H(2)O (4), have been synthesized and structurally characterized. The magnetic susceptibilities of the three heterometallic complexes have been investigated.
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Thin films of cobalt-iron cyanide (Co-Fe Prussian blue) have been fabricated by means of the modified Langmuir-Blodgett (LB) method using a smectite clay mineral (montmorillonite). In this combined method, clay LB films play a template role in the formation of the Co-Fe Prussian blue thin layer. The films were revealed to possess a well-organized structure not only in perpendicular directions to the film surface but also in parallel directions to the film surface. The photoinduced electron transfer from the iron ion to the cobalt through the bridging cyanide in the films occurred at low temperature (8 K), similar to that in the bulk Co-Fe Prussian blue. The films clearly exhibited magnetic anisotropy with regards to the direction of the applied magnetic field. Moreover, the photoinduced magnetization effect in the films was also found to be anisotropic.
The 1-D compound [Fe(L)(CN)2][Mn(hfac)2] (1), which adopts the -NC-Fe-CN-Mn- heterometallic structure, has been shown to exhibit light-induced excited spin-state trapping effects. After illumination, anti-ferromagnetic coupling was observed between the iron(II) (S = 2) and manganese(II) (S = 5/2) ions.
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is characterized as an important enzyme for protecting cells from oxidative stress-induced apoptosis and regulating the production of leukotrienes and prostanoids in cells overexpressing PHGPx. We studied whether the expression level of PHGPx fluctuates in polymorphonuclear leukocytes (PMNs) which were exposed to reactive oxygen species (ROS) and inflammatory cytokines at an inflammation site. Human peripheral PMNs up-regulated the expression level of PHGPx following culture with TNF-alpha, but not with IL-1beta, IL-8, and GRO. The up-regulated PHGPx expression was also observed in neutrophil-like cells that differentiated from the human leukemia cell line HL60 only after stimulation with TNF-alpha. However, macrophage-like differentiated HL60 cells and other cell lines, A498, ECV304, HeLa, U937, and HEK293, showed no increase in the PHGPx expression. This up-regulation of PHGPx was inhibited by treatment with the anti-oxidants, pyrrolidine dithiocarbamate, and N-acetyl-L-cysteine, and by inhibitors of NFkappaB and Src kinases. The stimulation of neutrophil-like differentiated HL60 cells with TNF-alpha induced activation of NFkappaB and c-Src kinase, and the activation was attenuated by treatment with the anti-oxidants. Up-regulation in neutrophil-like HL60 cells was also observed following exposure to H(2)O(2). These results indicate that activation of NFkappaB and/or Src kinases through ROS signaling may be involved in the up-regulation of the PHGPx in human PMNs stimulated by TNF-alpha.
Myosin-Va is an actin-based processive motor that conveys intracellular cargoes. Synaptic vesicles are one of the most important cargoes for myosin-Va, but the role of mammalian myosin-Va in secretion is less clear than for its yeast homologue, Myo2p. In the current studies, we show that myosin-Va on synaptic vesicles interacts with syntaxin-1A, a t-SNARE involved in exocytosis, at or above 0.3 microM Ca2+. Interference with formation of the syntaxin-1A-myosin-Va complex reduces the exocytotic frequency in chromaffin cells. Surprisingly, the syntaxin-1A-binding site was not in the tail of myosin-Va but rather in the neck, a region that contains calmodulin-binding IQ-motifs. Furthermore, we found that syntaxin-1A binding by myosin-Va in the presence of Ca2+ depends on the release of calmodulin from the myosin-Va neck, allowing syntaxin-1A to occupy the vacant IQ-motif. Using an anti-myosin-Va neck antibody, which blocks this binding, we demonstrated that the step most important for the antibody's inhibitory activity is the late sustained phase, which is involved in supplying readily releasable vesicles. Our results demonstrate that the interaction between myosin-Va and syntaxin-1A is involved in exocytosis and suggest that the myosin-Va neck contributes not only to the large step size but also to the regulation of exocytosis by Ca2+.
Two new cyano-bridged heterobinuclear complexes, [Mn(II)(phen)2Cl][Fe(III)(bpb)(CN)2] x 0.5CH3CH2OH x 1.5H2O (1) and [Mn(II)(phen)2Cl][Cr(III)(bpb)(CN)2] x 2H2O (2) [phen = 1,10-phenanthroline; bpb(2-) = 1,2-bis(pyridine-2-carboxamido)benzenate], and four novel azido-bridged Mn(II) dimeric complexes, [Mn2(phen)4(mu(1,1)-N3)2][M(III)(bpb)(CN)2]2 x H2O [M = Fe (3), Cr (4), Co (5)] and [Mn2(phen)4(mu(1,3)-N3)(N3)2]BPh4 x 0.5H2O (6), have been synthesized and characterized by single-crystal X-ray diffraction analysis and magnetic studies. Complexes 1 and 2 comprise [Mn(phen)2Cl]+ and [M(bpb)(CN)2]- units connected by one cyano ligand of [M(bpb)(CN)2]-. Complexes 3-5 are doubly end-on (EO) azido-bridged Mn(II) binuclear complexes with two [M(bpb)(CN)2]- molecules acting as charge-compensating anions. However, the Mn(II) ions in complex 6 are linked by a single end-to-end (EE) azido bridging ligand with one large free BPh4(-) group as the charge-balancing anion. The magnetic coupling between Mn(II) and Fe(III) or Cr(III) in complexes 1 and 2 was found to be antiferromagnetic with J(MnFe) = -2.68(3) cm(-1) and J(MnCr) = -4.55(1) cm(-1) on the basis of the Hamiltonian H = -JS(Mn)S(M) (M = Fe or Cr). The magnetic interactions between two Mn(II) ions in 3-5 are ferromagnetic in nature with the magnetic coupling constants of 1.15(3), 1.05(2), and 1.27(2) cm(-1) (H = -JS(Mn1)S(Mn2)), respectively. The single EE azido-bridged dimeric complex 6 manifests antiferromagnetic interaction with J = -2.29(4) cm(-1) (H = -JS(Mn1)S(Mn2)). Magneto-structural correlationship on the EO azido-bridged Mn(II) dimers has been investigated.
BACKGROUND: Little is known about the expression of receptor tyrosine kinases in adult soft tissue sarcomas (STS). In the current study, the authors analyzed the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in 281 patients with STS who were treated in a single institution. Verification of the presence of an association with prognosis was performed. METHODS: The current study included 281 adult patients with STS of the extremity and trunk who were diagnosed and treated in the National Cancer Center, Tokyo. Expression was assessed using immunohistochemical stains for EGFR, ERBB2, and KIT on formalin-fixed, paraffin-embedded tissue sections by standard avidin-biotin peroxidase complex technique and EGFR detection system. RESULTS: Positive staining of EGFR was observed in 168 of 281 (60%) patients. Positive staining was common in pleomorphic malignant fibrous histiocytomas (89%), myxofibrosarcomas (89%), synovial sarcomas (76%), malignant peripheral nerve sheath tumors (89%), and leiomyosarcomas (73%). It was less common in well differentiated liposarcomas (38%), fibrosarcomas (36%), and myxoid liposarcomas (6%). In contrast, positive staining of ERBB2 and KIT was very limited. Increased levels of EGFR were significantly associated with a decreased probability of overall survival (P = 0.01), although by univariate analysis; probability of overall survival at 5 years was 64% in patients with increased levels of EGFR and 79% in patients without such overexpression. The overexpression of EGFR was significantly associated with histologic grade (P < 0.001). Moreover, stratified log-rank test revealed that there is an interrelation between EGFR overexpression and histologic grade. CONCLUSIONS: EGFR overexpression was found to be a negative prognostic factor of adult STS, which is strongly associated with histologic grade. STS patients with EGFR overexpression may benefit from treatment with currently available biospecific inhibitors for EGFR.