Development of megakaryoblastic leukaemia in Runx1-Evi1 knock-in chimaeric mouse.
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Biomedical subjects
Publications and source records attributed to I Yamazaki.
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We have demonstrated for the first time the production of highly polarized short-pulse positrons with a finite energy spread in accordance with a new scheme that consists of two-quantum processes, such as inverse Compton scattering and electron-positron pair creation. Using a circularly polarized laser beam of 532 nm scattered off a high-quality, 1.28 GeV electron beam, we have obtained polarized positrons with an intensity of 2 x 10(4) e+ /bunch. The magnitude of positron polarization has been determined to be 73 +/- 15(stat) +/- 19(syst)% by means of a newly designed positron polarimeter.
For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.
The architecture of windmill hexameric zinc(II) -porphyrin array 1 is attractive as a light-harvesting functional unit in view of its three-dimensionally extended geometry that is favorable for a large cross-section of incident light as well as for a suitable energy gradient from the peripheral porphyrins to the meso-meso-linked diporphyrin core. Three core-modified windmill porphyrin arrays 2-4 were prepared for the purpose of enhancing the intramolecular energy-transfer rate and coupling these arrays with a charge-separation functional unit. Bisphenylethynylation at the meso and meso' positions of the diporphyrin core indeed resulted in a remarkable enhancement in the intramolecular S1-S1 energy transfer in 2 with tau=2 approximately 3 ps, as revealed by femtosecond time-resolved transient absorption spectroscopy. The fluorescence lifetime of the S2 state of the peripheral porphyrin energy donor determined by the fluorescence up-conversion method was 68 fs, and thus considerably shorter than that of the reference monomer (150 fs), suggesting the presence of the intramolecular energy-transfer channel in the S2 state manifold. Such a rapid energy transfer can be understood in terms of large Coulombic interactions associated with the strong Soret transitions of the donor and acceptor. Picosecond time-resolved fluorescence spectra and transient absorption spectra revealed conformational relaxation of the S1 state of the diporphyrin core with tau = 25 ps. Upon photoexcitation of models 3 and 4, which bear a naphthalenetetracarboxylic diimide or a meso-nitrated free-base porphyrin attached to the modified diporphyrin core as an electron acceptor, a series of photochemical processes proceeded, such as the collection of the excitation energy at the diporphyrin core, the electron transfer from the S1 state of the diporphyrin to the electron acceptor, and the electron transfer from the peripheral porphyrins to the diporphyrin cation radical, which are coupled to provide a fully charge-separated state such as that in the natural photosynthetic reaction center. The overall quantum yield for the full charge separation is better in 4 than in 3 owing to the slower charge recombination associated with smaller reorganization energy of the porphyrin acceptor.
BACKGROUND: Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role. METHODS AND RESULTS: Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by approximately 50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining ECs and decreased neointima formation. Progesterone did not influence the effects of estradiol on EC apoptosis. CONCLUSIONS: These results provide new insight into the cardioprotective action of estrogen as well as a paradigm of the response-to-injury hypothesis.
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Three different kinds of mixed self-assembled monolayers have been prepared to mimic photosynthetic energy and electron transfer on a gold surface. Pyrene and boron-dipyrrin were chosen as a light-harvesting model. The mixed self-assembled monolayers of pyrene (or boron-dipyrrin) and porphyrin (energy acceptor model) reveal photoinduced singlet-singlet energy transfer from the pyrene (or boron-dipyrrin) to the porphyrin on the gold surface. The boron-dipyrrin has also been combined with a reaction center model, ferrocene-porphyrin-fullerene triad, to construct integrated artificial photosynthetic assemblies on a gold electrode using mixed monolayers of the respective self-assembled unit. The mixed self-assembled monolayers on the gold electrode have established a cascade of photoinduced energy transfer and multistep electron transfer, leading to the production of photocurrent output with the highest quantum yield (50 +/- 8%, based on the adsorbed photons) ever reported for photocurrent generation at monolayer-modified metal electrodes and across artificial membranes using donor-acceptor linked molecules. The incident photon-to-current efficiency (IPCE) of the photoelectrochemical cell at 510 and 430 nm was determined as 0.6% and 1.6%, respectively. Thus, the present system provides the first example of an artificial photosynthetic system, which not only mimics light-harvesting and charge separation processes in photosynthesis but also acts as an efficient light-to-current converter in molecular devices.
A 66-year-old woman with aortic stenosis underwent an aortic root replacement with a composite graft and coronary artery reconstruction 2 years before presentation. On coronary angiography performed 2 years after operation, saphenous vein graft (SVG) to right coronary artery and SVG to first diagonal branch had both become totally occluded. SVG to left anterior descending artery showed 75% stenosis on the heel side of the distal anastomosis. The patient underwent a second coronary artery bypass via a left thoracotomy (the left internal thoracic artery was anastomosed to the first diagonal branch by interposing it with the left radial artery) and a small laparotomy (the right gastroepiploic artery was anastomosed to the right coronary artery) without a cardiopulmonary bypass. This approach is preferable to avoiding both a resternotomy and cardiopulmonary bypass in patients requiring repeat surgery.
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Tissue engineering can improve the former limitations of artificial organs. This article reports the long-term clinical results of grafts constructed with fragmented autologous adipose tissue. We did a retrospective analysis of a series of 53 patients with lower leg ischemia that received 69 fragmented adipose tissue (FAT) grafts implantation at our institution. The mean follow-up period was 36.0 months. After 1, 2, 3, and 5 years, the primary potency rates were 85.3, 83.3, 73.8, and 67.7%, respectively. The lumen of occluded areas not only at anastomotic sites but also in areas far from the anastomotic sites was occupied by a thickened neointima, which had a great number of capillary blood vessels, elastic laminae, smooth muscle cells, fibroblasts, and collagen fibers. This type of intimal hyperplasia was a characteristic finding in the FAT grafts. From the results of this clinical trial, we conclude that the FAT grafts are acceptable as vascular prostheses for ischemic lower extremities. The intimal hyperplasia at sites far from the anastomotic lines suggested the possibility of neointima formation throughout the luminal surface of the grafts.
Midterm observation of endovascular surgery using a fabric-covered stent graft for thoracic aortic aneurysms is discussed with postoperative follow-up findings based on regularly performed thoracic computed tomography (CT). From 1996 to 1999, 20 patients with thoracic aortic aneurysm underwent stent-graft placement in our hospital. One year follow-up CT results after placement were obtained for 17 patients. The CT scans found that there were both thrombosis and size reduction of aneurysm in 8 patients (46%), thrombosis without size reduction in 2 (13%), a new ulcerlike projection (ULP) in 3 (19%), persistent minor endoleakage in 2 (13%), a new endoleak in 1 (6%), and a recurrent endoleak from intercostal arteries in 1 (6%). The new ULP formation seemed to be a peculiar problem stemming from an intimal injury caused by edges of the stent. Therefore, we recently adopted a new spiral stent instead of the previous stent to avoid the injury. The new endoleak suggested that aneurysmal thrombosis without size reduction could cause the aneurysm to develop recurrent endoleaks. From these findings, we concluded that midterm observation of stent-graft repair for thoracic aortic aneurysms did not give satisfactory results. In order to improve the results of endovascular surgery using stent-grafts, we need to develop safer stent grafts with a reliable design to prevent endoleaks and to avoid intimal injury of the aorta. We also hope to develop effective technologies that can accelerate organization of thrombus in the aortic aneurysm after stent-graft placement.
To solve endoleakage problems of endovascular prostheses inserted in aortic aneurysms, a concept originating from tissue engineering was proposed. We proposed that in order to accelerate the thrombus inside the aneurysm, three major factors for successful tissue engineering, i.e., appropriate cells, extracellular matrices, and growth factors, should be introduced into a space between the endovascular grafts and the aneurysm. As a simulation model in animals, two kinds of fabric vascular prostheses were used. One was a small graft used as an endovascular graft and another was a large graft as an envelope for the small graft, used as the aneurysm wall. Adipose tissue fragments with fresh blood coagula were injected between the two grafts. The control was a preparation without tissue fragments. Two months and a half after surgery, the test group showed complete connective tissue formation in the space between the two grafts, but in the control, brownish thrombus remained. From this experiment, we speculated that tissue fragment transplantation will accelerate connective tissue formation of the thrombus, and this complete organization of the thrombus might reduce endoleakage.
Tendamistat is a strong inhibitory protein of porcine pancreatic alpha-amylase (PPA) with a K(i) value of 0.2 nM. To develop potent alpha-amylase inhibitors, we synthesized six odd-length cyclic peptides (5-15 residues) and four even-length cyclic peptides (10 and 12 residues) having the inhibitory sequence of tendamistat. Their PPA inhibitory activities were evaluated, and, among them, the 11-residue cyclic peptide Ten(15-23) (K(i) = 0.27 microM) exhibited the strongest inhibitory activity (K(i) = 0.27-1.41 microM). To examine the effect of cyclic structure on PPA inhibition, ten linear peptides corresponding to the cyclic peptides were also synthesized, and their PPA inhibitory activities were evaluated (K(i) = 0.28-1.00 microM). Interestingly, the 11-residue linear peptide Ten(15-23) exhibited almost the same inhibitory activity (K(i) = 0.28 microM) as that of cyclic Ten(15-23). The results of a circular dichroism study indicated that stabilization of the beta-hairpin structure occurred only for cyclic Ten(15-23). Also, the results of proteolytic digestion experiments of the cyclic and linear Ten(15-23) peptides by trypsin and chymotrypsin suggested no differences in protease resistance between the cyclic and linear structures. Therefore, we demonstrated that both cyclic and linear peptides containing the inhibitory sequence of tendamistat exhibit potent PPA inhibitory activity.
Corrected transposition of the great arteries without associated cardiac anomalies is a rare cardiac malformation. Few patients with this anomaly survive beyond 50 years of age because of systemic ventricular dysfunction or development of AV valvular regurgitation or conduction disturbance. We describe an autopsied, uncomplicated corrected transposition of the great arteries case in which the patient died at 84 years of age. We believe this patient to be the longest surviving corrected transposition of the great arteries associated person in the world.
A 65-year-old woman was admitted to the hospital because of anterior chest pain. Computed tomography and transthoracic 2-D echocardiogram demonstrated aortic valvular stenosis with calcification of whole aortic root. Cardiac catheterization study showed a transaortic pressure gradient of 73 mmHg and coronary angiography showed 75% stenosis at the right coronary ostia. Aortic valve replacement and coronary artery bypass grafting were planned. At operation, sinotubular junction and bilateral coronary ostia severely calcified with stenosis, prompted us to translocate the aortic valve with the composite graft, a 19 mm Bicarbon prosthesis and 25 mm woven Dacron graft. The postoperative course was uneventful. On cardiac catheterization done 27 days after operation, satisfactory valve motion and patent coronary bypass grafts were confirmed.
Three sets of dyads, in which a zinc-porphyrin (ZP) electron donor is connected to an aromatic diimide electron acceptor,either pyromellitimide (PI) or naphthalene-1,8:4,5-tetracarboxylic acid diimide (NI), via a boronate-ester bridge, a piperidine bridge, and a 1,3-dioxolane bridge, respectively, were prepared for the purpose of control of intramolecular electron transfer (ET) by acid-base reactions at the connecting bridge. Boronate-ester bridge is a Lewis acidic site and confers a chance to regulate intramolecular ET reaction upon base coordination. This has been demonstrated by suppression of photoinduced ET from ZP to PI or NI in highly electron-pair donating solvents or upon addition of a fluoride anion. To extend this strategy to control of ET-path selectivity, we prepared triad 18, which consists of a ZP donor bearing NI and PI acceptors at similar distances through a boronate-ester bridge and an acetal bridge, respectively. Photoexcitation of 18 in a free form led to intramolecular ET from (1)()ZP preferentially to NI, but the ET path was completely switched toward PI in F(-)-coordinated form without a serious drop in the rate, constituting a novel ET-switching molecular system.
The syntheses of soluble windmill and grid porphyrin arrays through the AgI-promoted coupling reaction of 1,4-phenylene-bridged linear porphyrin arrays, which are comprised of a central ZnII beta-free porphyrin and flanking peripheral NiII beta-octaalkylporphyrins, are described. The coupling reaction is advantageous in light of its high regioselectivity occurring only at the meso-position of the ZnII beta-free porphyrin as well as its easy extension to large porphyrin arrays. The windmill porphyrin arrays in turn serve as an effective substrate for further coupling reactions, to give three-dimensionally arranged grid porphyrin arrays. Further the grid porphyrin 12-mer (a tetramer of the linear porphyrin trimer) was also coupled to afford grid porphyrins (24-mer, 36-mer, and 48-mer). These porphyrin arrays were isolated in a discrete form by repetitive GPC/HPLC (GPC= gel-permiation chromatography). Competitive experiments with three linear porphyrin trimers bearing different peripheral metalloporphyrins (ZnII, NiII, and Cull), and the trapping experiment of the radical cation at the peripheral porphyrin with AgNO2, suggested that an initial one-electron oxidation of the easily oxidizable peripheral ZnII beta-octaalkylporphyrin with an AgI ion and a subsequent endothermic hole transfer assist the generation of the radical cation at the central ZnII beta-free porphyrin. In all ZnII-metallated windmill porphyrin arrays, the energy level of the S1 state of the meso-meso-linked diporphyrin core is lower than that of the peripheral porphyrins, thereby allowing an energy flow from the peripheral porphyrins to the central diporphyrin core; this has been confirmed by measurements of fluorescence lifetimes and picosecond time-resolved fluorescence spectra. The excitation energy transfer in the arrays encourages their potential use as an light-harvesting antenna.
BACKGROUND: Urine contains microscopically observable particles that can indicate certain types of disease in the urinary tract system. Determining these various types of sediments by manual operation is a cumbersome and time-consuming task. To eliminate this labor, we developed an automated urinary sediment analyzer with high-throughput pretreatment system. METHODS: The pretreatment system mainly consists of four reaction vessels for dying samples (urine), a sheath flow chamber, and an unique sample carrier mechanism from the reaction vessel to the flow chamber, which enables overlapped processing, and rapid transfer of samples with small dispersion and a short buildup time. RESULTS: The buildup time was experimentally found to be 1.8 s, and the extra-sample volume beside that for measurement was only 4.9 microl (1/20 of the total sample volume). CONCLUSIONS: Short buildup time results in high throughput of 120 samples per hour, and relatively small extra-volume contributes to reduce carryover.