Biomedical subjects
Publications and source records attributed to Naoto Ishikawa.
The presence of alkoxyl chains on the single-molecule magnet [(Pc')2Tb(III)] and its planar character favour its 2-D self-assembly on HOPG with the molecular plane parallel to the graphite surface, enabling us to control and/or predict the orientation of the preferential magnetization axis on the surface.
Alternating-current (ac) magnetic susceptibility measurements for tris(dipicolinato) complexes with a trivalent heavy lanthanide ion, [N(C2H5)4]3[Ln(dipic)(3)] x nH2O (dipic = pyridine-2,6-dicarboxylate; Ln = Tb, Dy, Ho, Er, Tm, or Yb) are reported. While none of the six complexes showed a magnetization lag from the ac magnetic field of 10-10(3) Hz above 1.8 K, the Dy, Er, and Yb complexes with odd numbers of 4f electrons exhibited the magnetization lag in a static magnetic field. This phenomenon is explained to be caused by the elimination of a fast relaxation path, which is only effective for the Kramers doublet ground states in near zero field. At higher static fields, the remaining paths such as Orbach and/or direct processes govern the dynamics of the two-level systems comprised of spin-up and spin-down states. The non-Kramers complexes were found to have a nondegenerate ground state with large energy gaps from higher states, which is consistent with their fast magnetization relaxation.
In Bordetella bronchiseptica, the functional type III secretion system (TTSS) is required for the induction of necrotic cell death in infected mammalian cells. To identify the factor(s) involved in necrotic cell death, type III-secreted proteins from B. bronchiseptica were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization tandem mass spectrometry. We identified a 69-kDa secreted protein designated BopC. The gene encoding BopC is located outside of the TTSS locus and is also highly conserved in both Bordetella parapertussis and Bordetella pertussis. The results of a lactate dehydrogenase release assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay demonstrated that BopC is required for necrotic cell death. It has been reported that tyrosine-phosphorylated proteins (PY) of host cells are dephosphorylated during B. bronchiseptica infection in a TTSS-dependent manner. We found that BopC is also involved in PY dephosphorylation in infected host cells. It appears that the necrotic cell death triggered by BopC occurs prior to the PY reduction in host cells, because Bordetella-induced cell death was not affected even in the presence of a dephosphorylation inhibitor. Furthermore, a translocation assay showed that the signal sequence for both secretion into culture supernatant and translocation into the host cell is located in 48 amino acid residues of the BopC N terminus. This report reveals for the first time that a novel type III effector, BopC, is required for the induction of necrotic cell death during Bordetella infection.
Leukocytapheresis (LCAP) is a therapeutic strategy for extra corporeal immunomodulation that has been used to treat several immunological disorders, including ulcerative colitis (UC), with encouraging results, inducing remission in steroid-resistant patients. However, we have experienced some complications during or after LCAP therapy. Common adverse effects include fever, chills, nausea, vomiting, and hypotension. One of the reasons for these adverse effects might be the use of nafamostat mesilate (NM) as an anticoagulant. In the present study, 75 patients with UC were divided into two groups, an NM group and a dalteparin sodium (DS) group. The clinical efficacy of these treatments, improvement after treatment, changes in leukocyte differential count, and adverse effects after LCAP therapy were then compared. The clinical efficacy, improvement after treatment, and changes in leukocyte classification were not significantly different between the two groups, while some adverse effects were observed in the NM group but not in the DS group. In conclusion, LCAP therapy is a useful therapy for patients with moderate to severe UC who fail to respond to glucocorticoid therapy, however, a safe anticoagulant should be used to avoid its related adverse effects.
We exploit a coherently excited nuclear wave packet to study nuclear motion modulation of electronic structure in a metal bridged phthalocyanine dimer, lutetium bisphthalocyanine, which displays two visible absorption bands. We find that the nuclear coordinate influences the energies of the underlying exciton and charge resonance states as well as their interaction; the interplay of the various couplings creates unusual anti-correlated spectral motion in the two bands. Excited state relaxation dynamics are the same regardless of which transition is pumped, with decay time constants of 1.5 and 11 ps. The dynamics are analyzed using a three-state kinetic model after relaxation from one or two additional states faster than the experimental time resolution of 50-100 fs.
Adrenomedullin (AM) administered intracolonically ameliorated the severity of acetic acid-induced colonic ulceration in rats. Ulcers were induced by subserosal injection of acetic acid into the colon. AM-treated group was administered 0.25-1.0 microg of AM in 0.5 ml of saline intracolonically once a day; the control group received only saline. AM administration dose-dependently and significantly reduced the size of the ulcerative lesions, the associated edema, and the infiltration of the affected area by inflammatory cells. AM also reduced tissue levels of interleukin-6, but not interferon-gamma. AM reduces the severity of acetic acid-induced colitis in rats, probably by inhibiting the production and/or release of Th-2 cell-derived factors such as interleukin-6.
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The first measurements of magnetization hysteresis loops on a diluted single crystal of [(Pc)2Ho]-.TBA+ (Pc = phthalocyaninato, TBA = tetrabutylammonium) in the subkelvin temperature range are reported. Characteristic staircase-like structure was observed, indicating the occurrence of the quantum tunneling of magnetization (QTM), which is a characteristic feature of SMMs. The quantum process in the new lanthanide SMMs is due to resonant quantum tunneling between entangled states of the electronic and nuclear spin systems, which is an essentially different mechanism from those of the known transition-metal-cluster SMMs. Evidence of the two-body quantum process was also observed for the first time in lanthanide complex systems.
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An alternating-current (ac) magnetic susceptibility measurement for the [(Pc)(2)Tb(III)](0) complex (Pc = phthalocyaninato) has shown that ligand oxidation of the anionic [(Pc)(2)Tb(III)](-) complex gives rise to a significant upward shift of the temperature range where the magnetization response shows a phase lag behind the time-varying external magnetic field. The peaks of the out-of-phase component of the ac susceptibility of the pi-radical [(Pc)(2)Tb(III)](0) were observed at 50, 43, and 36 K with ac magnetic fields of 10(3), 10(2), and 10 Hz, respectively, which were more than 10 K higher than the corresponding values of the anionic complex with a closed-shell pi-system. The ac susceptibility measurements on the complex with octa(dodecoxy)-substituted Pc ligand, which is readily dilutable in diamagnetic media, proved that the significant rise of the temperatures occurs as an intrinsic single-molecular property of the complex possessing both J = 6 and S = (1)/(2) systems, and is not due to long-range magnetic order or interactions between adjacent unpaired pi-electrons.
Two-color photon echo peak shift spectroscopy was used to study electronic coupling in a phthalocyanine homodimer. Two optical parametric amplifiers were used to produce pulses to excite the split lower states of LuPc2-. The existence of a two-color peak shift indicates the existence of correlation between these two dipole-allowed states. The nature of this correlation is discussed based on theoretical predictions of the interactions between exciton and charge resonance states.
A 19-year-old man with severe active ulcerative colitis was admitted to our hospital where he was prescribed 80 mg prednisolone and underwent leukocytapheresis (LCAP). Two weeks after initiating therapy, his symptoms had not recovered. We administered cyclosporin via continuous intravenous infusion for 12 days. Although his clinical symptoms improved, he complained of severe headache. Immediate plain computed tomography (CT) and magnetic resonance imaging angiography (MRA) revealed extensive thrombosis in the superior sagittal sinus and right transverse sinus. We treated this condition with the anticoagulant agent, heparin, which prevents and can treat venous thrombosis. We report an occurrence of cerebral sinus thrombosis accompanying ulcerative colitis, where active anticoagulant therapy was useful.
Double-decker phthalocyanine complexes with Tb3+ or Dy3+ showed slow magnetization relaxation as a single-molecular property. The temperature ranges in which the behavior was observed were far higher than that of the transition-metal-cluster single-molecule magnets (SMMs). The significant temperature rise results from a mechanism in the relaxation process different from that in the transition-metal-cluster SMMs. The effective energy barrier for reversal of the magnetic moment is determined by the ligand field around a lanthanide ion, which gives the lowest degenerate substate a large |Jz| value and large energy separations from the rest of the substates in the ground-state multiplets.
The f-electronic structures of the ground states of anionic bis(phthalocyaninato)lanthanides, [Pc(2)Ln](-) (Pc = dianion of phthalocyanine, Ln = Tb(3+), Dy(3+), Ho(3+), Er(3+), Tm(3+), or Yb(3+)), are determined. Magnetic susceptibilities of the powder samples of [Pc(2)Ln]TBA (TBA = tetra-n-butylammonium cation) in the range 1.8-300 K showed characteristic temperature dependences which resulted from splittings of the ground-state multiplets. NMR signals for the two kinds of protons on the Pc rings at room temperature were shifted to lower frequency with respect to the diamagnetic Y complex in Ln = Tb, Dy, and Ho cases, and to higher frequency in Er, Tm, and Yb cases. The ratios of the paramagnetic shifts of the two positions were near constant in the six cases. This indicates that the shifts are predominantly caused by the magnetic dipolar term, which is determined by the anisotropy of the magnetic susceptibility of the lanthanide ion. Using a multidimensional nonlinear minimization algorithm, we determined a set of ligand-field parameters that reproduces both the NMR and the magnetic susceptibility data of the six complexes simultaneously. Each ligand-field parameter was assumed to be a linear function of atomic number of the lanthanide. The energies and wave functions of the sublevels of the multiplets are presented. Temperature dependences of anisotropies in the magnetic susceptibilities are theoretically predicted for the six complexes.
The mature form of the vasodilator peptide adrenomedullin (AM-m) is synthesized from a glycine-extended precursor (AM-Gly) by enzymatic amidation. We have developed a highly sensitive enzyme immunoassay (Immune Complex Transfer Enzyme Immunoassay; ICTEIA) that enables us to measure levels of AM-Gly in plasma and tissue directly. The detection limit of this assay is 1 amol/assay, and the intra- and inter-assay precision are 4.5-14.1% and 9.9-20.5%, respectively. Dilution curves for plasma samples showed good linearity, and the analytical recovery was 107-116.6%. Using ICTEIA, we determined that the plasma concentration of immunoreactive AM-Gly is substantially higher than that of AM-m (5.22 +/- 2.56 vs. 1.21 +/- 0.79 fmol/ml). In contrast, levels of AM-Gly were much lower than those of AM-m in the lung, heart, kidney, adrenal gland and liver. We also evaluated AM-Gly and AM-m levels in rats in a morbid state induced by intraperitoneal administration of lipopolysaccharide (LPS). In most tissues, levels of AM-m and AM-Gly were both increased by LPS; however, AM-Gly/AM-m ratios were not significantly affected, which suggests that AM-Gly is rapidly converted to AM-m in tissue.
The first detection and characterization of the interactions between the f-electronic systems in the dinuclear complexes of paramagnetic trivalent Tb, Dy, Ho, Er, Tm, and Yb ions with phthalocyanine ligands are presented. The molar magnetic susceptibilities, chi(m), were measured for PcLnPcLnPc* ([Ln, Ln]; Pc = dianion of phthalocyanine, Pc* = dianion of 2,3,9,10,16,17,23,24-octabutoxyphthalocyanine) and PcLnPcYPc* ([Ln, Y]) in the range from 1.8 K to room temperature. The selective synthetic method previously reported for the heterodinuclear complex [Y, Ln] was used to prepare [Ln, Ln] and [Ln, Y] with a modification on the choice of starting materials. The f-f interaction contributions to the magnetic susceptibility are evaluated as Delta(chi)(m)T = chi(m)([Ln, Ln])T - chi(m)([Ln, Y])T - chi(m)([Y, Ln])T, where T refers to temperature on the kelvin scale. The homodinuclear complexes having f(8)-f(10)-systems, namely [Tb, Tb], [Dy, Dy], and [Ho, Ho], show positive Delta(chi)(m)T values in the 1.8-50 K range, indicating the existence of ferromagnetic interaction between the f-systems. The magnitude of the Delta(chi)(m)T increases in the descending order of the number of f-electrons. [Er, Er] gives negative Delta(chi)(m)T values in the 1.8-50 K range, showing the antiferromagnetic nature of the f-f interaction. [Tm, Tm] exhibits small and negative Delta(chi)(m)T values, which gradually decline in the negative direction as the temperature decreases in the range 13-50 K and sharply rise in the positive direction as the temperature falls from 10 to 1.8 K. [Yb, Yb] has extremely small Delta(chi)(m)T values, whose magnitude at 2 K is less than 1% of that of [Tb, Tb]. The ligand field parameters of the ground-state multiplets of the six [Ln, Y] complexes are determined by simultaneous fitting to both the magnetic susceptibility data and paramagnetic shifts of (1)H NMR. The theoretical analysis successfully converged by assuming that each ligand field parameter is a function of the number of f-electrons in each ion. Using these parameters as well as the previously obtained corresponding parameters for the [Y, Ln] series, the interactions between the f-systems in [Ln, Ln] are investigated. All the characteristic observations above are satisfactorily reproduced with the assumption that the magnetic dipolar term is the sole source of the f-f interaction.
Several cofacial phthalocyanines (Pcs) with an Si-Si linkage were obtained by one-step condensation of 1H-isoindole-1,3(2H)-diimine with hexachlorodisilane as template in quinoline. They were characterized by gel-permeation chromatography, IR, NMR spectroscopy, and mass spectrometry, and cyclic voltammetry. The results strongly suggest that we indeed obtained Pc dimers directly linked by an Si-Si bond using this novel concept of utilizing a compound/salt with an element-element bond as a template. The cofacial dimer structures are reasonably supported by X-ray absorption near-edge structure (XANES), electronic absorption and magnetic circular dichroism (MCD) spectra, and molecular orbital (MO) calculations. Interestingly, they show an electronic absorption spectrum very similar to that of silicon tetrabenztriazacorrole (SiTBC).
We report a patient with protein-losing gastropathy probably associated with autoimmune disease, in whom prednisolone treatment was highly effective. A 45-year-old woman was admitted to our hospital with edema of the face and lower extremities. Blood examination revealed hypoproteinemia, hypoalbuminemia, and hypercholesteremia. Renal biopsy revealed no definite findings of lupus nephritis, including vasculitis. A diagnosis of protein-losing gastropathy was made on the basis of increased alpha1-antitrypsin clearance and 99mTc-labeled human serum albumin scintigram showing abnormal radioactivity in the stomach. Endoscopic gastric biopsies revealed nonspecific inflammation, but marked intramural edema. Based on a slight elevation of antinuclear antibody level, autoimmune disease was suspected to be involved in this patient. Administration of prednisolone, as a diagnostic therapy, alleviated the hypoproteinemia, hypoalbuminemia, and hypercholesteremia. These findings suggest that an autoimmune mechanism could have been involved in this case of protein-losing gastropathy.