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Biomedical subjects

Takuya Matsumoto

Publications and source records attributed to Takuya Matsumoto.

33 records · Page 2Linked to original sources

A dodecameric porphyrin wheel.

A dodecameric porphyrin wheel was prepared by Ag(I)-promoted intramolecular coupling of a linear porphyrin dodecamer and was observed by scanning tunneling microscopy (STM). Efficient energy hopping along the array was revealed by femtosecond transient anisotropy measurements.

Biomimetic Materials↗

Osteopontin-derived peptide SVVYGLR induces angiogenesis in vivo.

Our previous study reported that an osteopontin-derived peptide SVVYGLR activates the adhesion, migration and tube formation abilities of endothelial cells in vitro. The present study investigated angiogenesis due to synthetic SVVYGLR and mutant peptides in vivo. Mutant peptides (n = 7) were synthesized by substituting alanine (A) for one of the 7 amino acids comprising SVVYGLR. In dorsal air sac assay, mouse dorsal skin 5 days after implantation of a chamber filled with SVVYGLR had approximately the same number of newly formed blood vessels to that filled with vascular endothelial growth factor (VEGF). The ability of angiogenesis due to SVVAGLR was significantly lower than that due to other 6 mutant peptides and SVVYGLR. This indicates that tyrosine (Y) plays an important role in angiogenesis due to SVVYGLR.

Amino Acid Motifs↗

One-dimensional CuBr4(2-) ion array and CuBr3- ion chain included in the pi conducting framework composed of bis(methylthio)tetrathiafulvalenothioquinone-1,3-dithiocarbonatodithiolemethide molecules.

The reaction of a new donor molecule having a planar but largely bent skeleton, bis(methylthio)tetrathiafulvalenothioquinone-1,3-dithiocarbonatodithiolemethide (1), with CuBr(2) in CH(3)CN/CS(2) afforded a black-colored crystal with a formula of 1(4).CuBr(4).2CuBr(3). In the crystal 1 molecules are one-dimensionally stacked to form half-cut pipelike columns, which are arranged to construct two different shapes of channels included by a one-dimensional array of CuBr(4)(2)(-) ions and a bibromide-bridged linear chain of CuBr(3)(-) ions with a square-pyramidal geometry at the Cu atom, [CuBr(3)(-)](n)(), respectively. The room-temperature electrical conductivity on the single crystal of 1(4).CuBr(4).2CuBr(3) was 2.0 x 10(-)(2) S cm(-)(1), and the temperature dependence of electrical conductivity was semiconducting with a large activation energy of 160 meV. The interactions between the neighboring Cu(II) d spins in the one-dimensional S = 1/2 spin systems due to CuBr(4)(2)(-) ions and CuBr(3)(-) ions in [CuBr(3)(-)](n)() were both antiferromagnetic, and the magnitudes were moderate (Weiss temperature, THETAV; = -18 K) in the former spin system and fairly large (coupling constant, J/k(B) = -120 K) in the latter spin system, which was in marked contrast to a moderate and ferromagnetic [CuBr(3)(-)](n)() chain in the cyclohexylammonium salt already known.

Journal Article↗

Angiogenic activity of osteopontin-derived peptide SVVYGLR.

Angiogenesis plays an important role in various pathological conditions as well as some physiological processes. Although a number of soluble angiogenic factors have been reported, extracellular matrix also has crucial effect on angiogenesis through interaction with endothelial cells. Since recent reports showed osteopontin had some angiogenic activity, the effect of the SVVYGLR peptide, novel binding motif in osteopontin molecule, on angiogenesis was examined in this study. Synthetic peptide SVVYGLR did not have proliferative effect on endothelial cells but adhesion and migration activity to endothelial cells. Furthermore, SVVYGLR had as potent activity for tube formation in three-dimensional collagen gel as vascular endothelial growth factor which is known to be the strongest angiogenic factor. Electron microscopical analysis showed a number of microvilli on the endothelial luminar surface and tight junction formation in the luminar intercellular border between endothelial cells, indicating SVVYGLR induced cell porarity and differentiation of endothelial cells. This small peptide might be expected to stimulate angiogenesis to improve some ischemic conditions in the future because of some advantages due to smaller molecular weight.

Amino Acid Sequence↗

Electrical conducting and magnetic properties of (ethylenedithiotetrathiafulvalenothioquinone-1,3-diselenolemethide)2.FeBr4 (GaBr4) crystals with two different interlayer arrangements of donor molecules.

Two donor molecules newly synthesized, dimethylthio- and ethylenedithio-tetrathiafulvalenothioquinone-1,3-diselenolemethides (1 and 2), were used to prepare their charge-transfer (CT) salts with a magnetic FeBr(4)(-) counteranion. For 1, a low electrical conducting 1:1 salt (1.FeBr(4)) was obtained, in which molecules of 1 are tightly dimerized in a one-dimensional (1D) stacking column. On the other hand, 2 gave a 2:1 salt (2(2).FeBr(4)) as two different kinds of plate crystals (I and II). Both I and II possess similar stacking structures of molecules of 2 in each 1D column with a half-cut pipelike structure along the c axis. However, for I, the stacking columns are aligned in the same direction along the a and b axes, while for II they are in the same direction along the a axis, but in the reverse direction along the b axis, resulting in the difference in the relative arrangement of molecules of 2 and FeBr(4)(-) ions between the two crystals. The room-temperature electrical conductivities of the single crystals of I and II were 13.6 and 12.7 S cm(-)(1), respectively. The electrical conducting behavior in I was metallic above 170 K but changed to be semiconducting with a very small activation energy of 7.0 meV in the temperature range 4-170 K. In contrast, II showed the semiconducting behavior in the whole temperature range 77-285 K. The corresponding nonmagnetic GaBr(4)(-) salts with almost the same crystal structure as I and II showed definitively different electrical conducting properties in the metal to semiconductor transition temperature in I as well as in the magnitude of activation energy in the semiconducting region of I and II. The interaction between the d spins of FeBr(4)(-) ions was weak and antiferromagnetic in both I and II, but the magnitude of the spin interaction was unexpectedly larger compared with that in the FeBr(4)(-) salt of the corresponding sulfur derivative of 2 with closer contact between the neighboring FeBr(4)(-) ions. These electrical conducting and magnetic results suggest a significant interaction between the conducting pi electrons and the d spins of FeBr(4)(-) ions located near the columns or layers.

Journal Article↗

Effects of single and repeated prolonged stress on mu-opioid receptor mRNA expression in rat gross hypothalamic and midbrain homogenates.

This study tested the hypothesis that stress-induced opioid peptides may have stimulative and inhibitive influence on mu opioid receptor (MOR) mRNA expression and hypothalamus. Several studies have investigated the effects of stress on MOR mRNA expression in rat brain, but almost none compared the response to single versus repeated stresses. Here, we examined the effects of single and repeated stress on MOR mRNA expression in different rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 h (1R) or 4 h per day on 2 (2R) or 3 (3R) consecutive days, the hypothalamus and midbrain were removed immediately and MOR mRNA levels in both regions were determined by RT-PCR. Blood samples were also collected for simultaneous measurement of serum adrenocorticotropic hormone (ACTH) and corticosterone (CS). MOR mRNA expression was significantly higher in both regions in the 2R group, whereas expression levels in the 3R group did not differ from controls. In the 1R group, hypothalamic MOR expression was equivalent to that in controls, but expression was significantly higher in the midbrain. Serum ACTH levels were significantly higher only in the 1R group, whereas serum CS was significantly higher in both the 1R and 3R groups. Our findings indicate that the influence of restraint stress on MOR mRNA expression in the hypothalamus is different than in the midbrain region in rats. Endogenous opioid peptides released in response to stress may paradoxically have an effect on the HPA axis.

Animals↗

Protective effect of chronic vitamin C treatment on endothelial function of apolipoprotein E-deficient mouse carotid artery.

Endothelium-dependent relaxations are impaired in carotid artery of apolipoprotein E-deficient (apoE-/-) mice. This impairment seems to be due to increased formation of superoxide anions and inactivation of endothelial nitric oxide (NO). In the present study, we tested hypothesis that chronic treatment with vitamin C may prevent endothelial dysfunction by increasing release of NO from endothelial cells. C57BL/6 and apoE-/- mice were treated for 26 weeks with Western-type fat diet with and without 1% vitamin C. Vasomotor function of isolated carotid arteries was studied by video dimension analyzer. Expression of endothelial NO synthase (eNOS) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) protein were evaluated by Western blotting. Levels of cGMP and cAMP were measured by radioimmunoassay. In apoE-/- mice, vitamin C significantly augmented relaxations to acetylcholine (10-9-10-5 mol/l), but did not affect relaxations to NO donor diethylammonium-(Z)-1-(N,N-diethylamino) diazen-1-1,2-diolate (DEA-NONOate; 10-9-10-5 mol/l). In contrast, vitamin C reduced relaxations to acetylcholine and DEA-NONOate in C57BL/6 mice. Interestingly, vitamin C significantly increased basal cGMP levels in C57BL/6 mice but did not affect cGMP formation in apoE-/-. Vitamin C treatment did not affect expression of eNOS protein, whereas elevated expression of PECAM-1 protein in apoE-/- mice was returned to normal level. Our findings demonstrate that chronic treatment with vitamin C prevents endothelial dysfunction of carotid artery induced by hypercholesterolemia. This effect seems to be mediated by preservation of NO bioavailability in endothelial cells.

Animals↗

Effects of odorants on the hypothalamic-pituitary-adrenal axis and interleukin-6 (IL-6) and IL-6 receptor mRNA expression in rat hypothalamus after restraint stress.

We recently reported that stress alters interleukin (IL)-6 and IL-6 receptor (IL-6R) mRNA levels in the hypothalamus. Odorants are reported to exert anti-stress effects. The aim of our study was to determine the effects of odorants on IL-6 and IL-6R mRNA expression in the hypothalamus, using reverse transcriptase-polymerase chain reaction and on serum levels of adrenocorticotropic hormone (ACTH) and corticosterone in rats exposed to stress. Control rats were not exposed to stress; test control rats were exposed to 4 h stress then immediately killed. In other groups, rats were exposed to the same stress followed by 30 min exposure air, dimethoxymethylbenzene (DMMB), or citralva. In the air group, IL-6 and IL-6R mRNA levels were significantly reduced and serum levels of ACTH and corticosterone significantly increased relative to the control. Exposure to DMMB significantly augmented IL-6 mRNA expression but restored that of IL-6R mRNA, did not change serum corticosterone level relative to that of the air group and significantly reduced ACTH. In comparison, citralva restored the expression of IL-6 and IL-6R mRNAs and significantly increased serum ACTH and corticosterone levels. Our results indicate that citralva enhances stress-induced activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone (CRH)-mediated stimulation of IL-6, while DMMB enhances the beneficial action of IL-6 without affecting CRH.

Animals↗

Control of pore size in L-lactide/epsilon-caprolactone copolymer foams for tissue regeneration by the freeze-drying method.

In the regeneration and repair of missing tissues, synthetic polymer scaffolds need many pores to involve cells and to supply cells with nutrients. The control of the pore size of biodegradable L-lactide/epsilon-caprolactone copolymer foams was studied by changing the polymer concentration and the cooling temperature in the freeze-drying method. The mixtures of polymer and 1, 4-dioxane solution were poured into an 18-8 stainless steel Petri dish and frozen. The pore size of a polymer foam tends to increase from the bottom towards the top of a Petri dish. The pore size decreased to one-half with increasing polymer concentration (1 to 10 wt%). The mean pore size in foams of 8% polymer concentration decreased from 100 microm to 20 microm as cooling temperature was lowered. This suggests that the higher cooling rate due to lower cooling temperature can produce smaller ice-crystals and result in smaller pores.

Absorbable Implants↗

Metallic conductivity and ferromagnetic interaction of iron(III) d spins in the needle crystals of (ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide)(2).FeBr(4) salt.

The 2:1 charge-transfer (CT) salts (1(2).FeBr(4) and 1(2).GaBr(4)) of ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide (1) with FeBr(4)(-) and GaBr(4)(-) counteranions were obtained as needle crystals, whose structures are almost the same as each other. The 1 molecules form a one dimensionally stacked column with alternation of their molecular axis direction, while the counteranions are aligned in parallel with the 1-stacked columns with the direction of their distorted-tetrahedral geometry maintained. The room-temperature electrical conductivities measured on the single crystals of 1(2).FeBr(4) and 1(2).GaBr(4) were 4.6 and 2.1 S cm(-1), respectively. From the temperature dependences of their electrical conductivities in both cases the electrical conducting properties were metallic between ca. 170 and 300 K, but below ca. 170 K converted to be semiconducting and continued till 5 K, although the activation energies are very small (4-10 meV). For 1(2).FeBr(4) very weak and antiferromagnetic interaction occurred between the d spins of FeBr(4)(-) ions in the temperature range of ca. 1-300 K. However, below ca. 15 K the ferromagnetic interaction was reversely preferential possibly by participation of the pi spin of 1.

Journal Article↗

Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries.

BACKGROUND: Transcription factor activator protein-1 (AP-1) is activated and upregulated in injured arterial smooth muscle cells in vivo, yet the exact role of the AP-1--related pathway in vascular disease in vivo has remained unclear. We examined the role of the transfer of synthetic double-stranded cis-element decoy oligodeoxynucleotides (ODNs) in balloon-injured rabbit carotid arteries and the effects of these ODNs on neointimal thickening. METHODS AND RESULTS: Transfection of fluorescein isothiocyanate--labeled ODNs using the hemagglutinating virus of Japan liposome method resulted in widespread distribution of fluorescent nuclear signals over the entire medial layer in injured arteries. Gel mobility shift assay revealed that AP-1 DNA binding was activated and that the AP-1 decoy reduced AP-1 DNA binding activity as a result of specific binding affinity to AP-1 in vivo. In morphometric analyses, AP-1 decoy led to a significant reduction in the neointimal area and a significant reduction in cell number and transforming growth factor-beta(1) production of human aortic smooth muscle cells under conditions of platelet-derived growth factor stimulation. CONCLUSIONS: Because AP-1 decoy transfection in vivo dramatically prevented neointimal thickening in balloon-injured arteries, AP-1 may be a useful molecular target for gene therapy to reduce restenosis.

Adult↗

Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit: a limited biological effect as a result of the loss of medial smooth muscle cells.

BACKGROUND: The intimal hyperplasia of vein grafts is a major cause of late graft failure and is more pronounced under hyperlipidemia. We previously reported that endothelial cell (ec)-type nitric oxide synthase (NOS) gene transfer inhibited graft intimal hyperplasia under poor runoff conditions. However, little information is available on either ecNOS gene transfer or intimal thickening under hypercholesterolemia. METHODS: Using the hemagglutinating virus of Japan liposomes, bovine ecNOS complentary DNA (5000 hemagglutinating activity units/mL) was transfected intraluminally to the right jugular vein, and these veins were then implanted as reversed vein grafts in an end-to-side fashion to the ipsilateral carotid artery. RESULTS: The cyclic guanosine 3',5'-monophosphate content of the ecNOS vein significantly increased in the grafts at 4 days after gene transfer, but the levels were only 25% greater than those found in the untreated veins. An immunohistochemical analysis at the same time suggested a large loss of medial smooth muscle cells that might have led to a reduction in the exogenous gene expression. The neointima of the ecNOS grafts was significantly reduced 4 weeks after implantation (P <.05), but the effect of ecNOS was limited to about a 30% inhibition. This reduction was associated with a reduced population of proliferating cells and decreased macrophage accumulation in the graft wall. CONCLUSIONS: These results demonstrated that the ecNOS gene transfer suppressed intimal hyperplasia of the vein grafts under hyperlipidemic conditions. However, this effect may be limited because of the smooth muscle cell loss related to the use of an intraluminal delivery methods. These data lead to speculation that the outcome of ecNOS gene transfer could be improved using different methods of gene delivery.

Animals↗

Effects of single and repeated restraint stresses on the expression of beta(1)-adrenoceptor mRNA in the rat hypothalamus and midbrain.

We examined the effects of single and repeated restraint stresses on the expression of beta(1)-adrenoceptor mRNA in the rat midbrain and hypothalamus using reverse transcriptase-polymerase chain reaction (RT-PCR). After the rats had been restrained for 4 h (single stress), or for 4 h per day during 2 or 3 consecutive days, the hypothalamus and midbrain were removed immediately and beta(1)-adrenoceptor mRNA levels in these regions were determined by RT-PCR. Single stress significantly decreased the mRNA level in the hypothalamus, but the mRNA level was near control levels after 2 and 3 days of stress. In the midbrain, single stress had no effect on the mRNA level, but 2 days of stress significantly increased it.

Animals↗