Protein modification by a Maillard reaction intermediate methylglyoxal. Immunochemical detection of fluorescent 5-methylimidazolone derivatives in vivo

Methylglyoxal (MG), an endogenous metabolite that increases in diabetes, is a common intermediate in nonenzymatic glycation (Maillard reaction) in vivo. Here we describe the immunochemical approach to the detection of MG adducts in proteins in vitro and in atherosclerotic lesions of human aorta in vivo. The reaction of protein (bovine serum albumin) with MG led to selective loss of arginine and lysine residues, accompanied by the formation of 5-methylimidazolone (N delta-(5-methylimidazolon-2-yl)ornithine) and imidazolysine (1,3-di-lysino-4-methylimidazole) derivatives, respectively. The anti-5-methylimidazolone antibody was prepared by immunizing rabbits with a MG-keyhole limpet hemocyanin conjugate and purifying the serum on an affinity gel prepared by covalent attachment of the 5-methylimidazolone derivative. The antibody cross-reacted with the proteins treated with not only MG but trioses, such as hydroxyacetone, dihydroxyacetone, and glyceraldehyde. The immunohistochemical analysis revealed that atherosclerotic lesions of human aorta contained 5-methylimidazolone derivatives whose distributions were identical to those of advanced glycation end products (AGEs) detected by the anti-AGE antibody.     

Effects of Digital Doping of Mn on Giant Magneto-Optical Properties of Zn1−x Mn x Se Quantum Wells

We have studied effects of the digital-doping profile of MnSe layers on the giant magneto-optical properties in Zn_1?x Mn _x Se-based quantum wells. The giant Zeeman shift energy increases monotonically with increasing spatial overlap of the exciton wavefunction with the 0.5 monatomic-thick effective Mn layers at the interfaces between the digitally doped MnSe layers and nonmagnetic ZnSe layers. Also, a field-induced enhancement factor of the excitonic photoluminescence intensity, because of the suppression of the exciton energy transfer into the d-d transition of Mn-ions, increases linearly with increasing such overlap of the exciton wavefunction with the effective Mn layer. In addition, the formation energy as large as 18.6 meV and the formation time of the magnetic polaron are determined, which are also affected by the digital-doping profile.     

Combined pars plana vitrectomy, lens removal and intraocular lens implantation for complications of diabetic retinopathy. Surgical results in 120 cases

We performed combined vitrectomy, lens removal and posterior chamber intraocular lens implantation for proliferative diabetic retinopathy in 120 eyes of 101 patients. Follow-up periods ranged from 3 to 63 months, with a mean of 17 months. Three lens removal methods were used: extracapsular cataract extraction (14 eyes), phacoemulsification and aspiration (49 eyes), and pars plana phacoemulsification (57 eyes). Preoperative rubeosis iridis or neovascular glaucoma was found in 21 eyes. Gas or temporary silicone oil tamponade was employed in 32 eyes. Surgical results were good, and the postoperative vision was finger counts or below only in 13 eyes. Thus the combined surgery proved to have no serious problems. Our results indicate two important points. (1) It is best to chose either of the following two methods for the lens surgery: phacoemulsification with continuous circular capsulorhexis, self sealing sclerocorneal incision, and in-the-bag fixation of the posterior chamber lens, or pars plana phacoemulsification leaving the anterior capsule, rub off and aspirating the lens epithelial cells, continuous circular capsulorhexis, and posterior chamber lens implantation in front of the anterior capsule from a self-sealing sclerocorneal wound. (2) It is mandatory to do complete vitrectomy and cut out the vitreous gels incarcerated in the sclerotomy site.     

Transformation and fragmentation behavior of molten metal drop in sodium pool

In order to clarify the fragmentation mechanism of a metallic alloy (U–Pu–Zr) fuel on liquid phase formed by metallurgical reactions (liquefaction temperature = 650 °C), which is important in evaluating the sequence of core disruptive accidents for metallic fuel fast reactors, a series of experiments was carried out using molten aluminum (melting point = 660 °C) and sodium mainly under the condition that the boiling of sodium does not occur. When the instantaneous contact interface temperature (T_i) between molten aluminum drop and sodium is lower than the boiling point of sodium (T_c,bp), the molten aluminum drop can be fragmented and the mass median diameter (D_m) of aluminum fragments becomes small with increasing T_i. When T_i is roughly equivalent to or higher than T_c,bp, the fragmentation of aluminum drop is promoted by thermal interaction caused by the boiling of sodium on the surface of the drop. Furthermore, even under the condition that the boiling of sodium does not occur and the solid crust is formed on the surface of the drop, it is confirmed from an analytical evaluation that the thermal fragmentation of molten aluminum drop with solid crust has a potential to be caused by the transient pressurization within the melt confined by the crust. These results indicate the possibility that the metallic alloy fuel on liquid phase formed by the metallurgical reactions can be fragmented without occurring the boiling of sodium on the surface of the melt.     

The integral experiment on beryllium with D-T neutrons for verification of tritium breeding

A clean benchmark experiment on beryllium was performed with D-T neutrons at the FNS facility of the Japan Atomic Energy Agency. The main objective was to verify the integral data related to the tritium production on lithium isotopes. Tritium production rates, as well as activation reaction rates were measured inside the beryllium assembly that was shaped as a pseudo-cylindrical slab with an area-equivalent diameter of 628 mm and a thickness of 355 mm. Experimental results were analyzed with a three-dimensional Monte Carlo transport code MCNP-4C and FENDL/MC-2.0, JENDL-3.2/3.3 neutron transport libraries. Evaluation of reaction rates was based on the cross section data taken from the JENDL Dosimetry File and ENDF B-VI data libraries. Analysis shows that all calculation combinations (transport and activation cross section libraries) used for evaluation of reaction rates give data that is agreeable with measured values within 10%.     

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

Paxillin isoforms in mouse. Lack of the gamma isoform and developmentally specific beta isoform expression

Paxillin, a focal adhesion protein, exists as multiple isoforms in humans (alpha, beta, and gamma). To understand more about the physiological role of each isoform, we have employed the mouse system. We found that although the alpha and beta isoforms are present in the mouse, the gamma isoform is not. The alpha isoform protein was detected clearly in most adult tissues, whereas the beta isoform protein was almost undetectable except in spleen, testis, thymus, and lung. On the other hand, mRNAs of both isoforms were detectable in all tissues we examined. High levels of the beta isoform protein was detected in peritoneal exudate macrophage cells in adult mouse as well as in cultured fibroblasts, together with the alpha isoform. The alpha isoform was expressed at a constant level throughout the embryonic stages we examined, whereas the beta isoform protein was detected at the mid-stages of development and increased to levels almost equal to those of the alpha isoform during the late stages of embryogenesis. Therefore, unlike the alpha isoform, expression of the beta isoform protein is restricted in adult tissues. Moreover, we showed that alpha and beta isoforms were colocalized within the same focal adhesion plaques, and cytoplasmic pools of both isoforms exist in the perinuclear area, colocalized with the Golgi apparatus.     

Robust digital control of a DC–DC buck converter with low frequency samplings

A robust DC?CDC converter which can covers extensive load change and also input voltage changes with one controller is needed. Then the demand to suppress output voltage change becomes still severer. We propose an approximate 2-degree-of-freedom (2DOF) digital controller which realized start-up response and dynamic load response independently. The controller makes a control bandwidth wider, and at the same time makes variations of the output voltage small at sudden changes of a load and an input voltage. In this paper, a new approximate 2DOF digital control system with additional zeros is proposed. Using the additional zeros, the second-order differential transfer characteristics between equivalent disturbances and a output voltage are realized. Therefore, the new controller makes variations of the output voltage smaller and the sudden changes of the load and the input voltage. This controller is actually implement on a DSP and is connected to the DC?CDC converter. Experimental results demonstrate that this type of digital controller can satisfy given severe specifications with low frequency sampling.