Identification of pentosidine as a native structure for advanced glycation end products in beta-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis

beta-2-Microglobulin (beta-2m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA). Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta-2m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta-2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in beta-2m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived beta-2m-containing amyloid fibrils to the pathogenesis of DRA.     

A study of multiple biomarkers in coke oven workers--a cross-sectional study in China

We conducted a cross-sectional molecular epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of internal dose, leukocyte aromatic DNA adducts as markers of biologically effective dose, serum p53 protein as a response marker and genetic polymorphisms of cytochrome P4501A1 and glutathione S-transferase MI as susceptibility markers. Twenty-five male subjects each were randomly selected from the top, middle and bottom work areas of the oven, and the control plant. They were matched for age and smoking status. The mean levels of PAH exposure, monitored by stationary and personal samplers, and of worker urinary 1-hydroxypyrene differed significantly between the top, middle and bottom of the oven and control work areas. The highest stationary and personal PAH concentrations and 1-hydroxypyrene levels were demonstrated at the top work area. Good correlations were found between the stationary PAH levels, personal PAH levels and urinary 1-hydroxypyrene levels. No positive correlations were demonstrated between aromatic DNA adduct levels and current or cumulative PAH exposure dose. In the presence of genetic polymorphisms of cytochrome P4501A1, a positive correlation was demonstrated between aromatic DNA adducts and urinary 1-hydroxypyrene levels. There was also a significant correlation between serum p53 protein levels and the cumulated benzo[a]pyrene exposure dose. Although these biomarkers have certain limitations, they are applicable to cancer epidemiology, and may contribute to our understanding of the mechanisms of carcinogenesis.     

Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway

Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK. We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1. Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast. In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2. In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged. These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers.     

An autopsy case of adult onset glycogen storage disease type Ia

A 3-week tour of the Far East was coordinated by Dr. Ronald DeWald, senior travelling fellow appointed by the Scoliosis Research Society. Three junior fellows appointed by the Education Committee of the Scoliosis Research Society accompanied him. The purpose of this fellowship was to develop a comaraderie and exchange ideas, thoughts, and experiences in the field of spinal deformity.     

G-CSF increases secretion of urokinase-type plasminogen activator by human lung cancer cells

AIMS: To examine the feasibility of using the human iris in vivo for the assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of MAO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral doses of moclobemide, a selective MAO-A inhibitor, and selegiline, a selective MAO-B inhibitor, on mydriatic responses to tyramine. METHODS: Twelve healthy male volunteers participated in three monthly sessions, each associated with ingestion of one capsule (moclobemide 450 mg, selegiline 10 mg, or placebo), according to a double-blind, balanced, cross-over design. Tyramine hydrochloride eye-drops (75 mM, 2 x 10 microl) were instilled three times in the left conjuctival sac at 40 min intervals. Pupil diameter was monitored with a binocular infrared television pupillometer before and for 4.5 h after ingestion of the capsule. The pupillary response to tyramine was expressed as the area under the pupil diameter x time curve (arbitrary units). A blood sample was taken before and 2 h after ingestion of the capsule, for the assay of platelet MAO-B activity, and plasma 3,4-dihydroxyphenylglycol (DHPG) concentration, an index of MAO-A activity. Platelet MAO activity was assayed radiochemically, using [14C]-phenylethylamine as substrate, and plasma DHPG by high performance liquid chromatography (h.p.l.c.). The results were analysed using analysis of variance with repeated measures, followed by Bonferroni's corrected t-test, using a significance criterion of P < 0.05. RESULTS: Both moclobemide and selegiline, compared with placebo, caused significant miosis in the right (untreated) eye. The changes in pupil diameter (mm +/- s.e. mean) from the pretreatment measurement were: placebo -0.09 +/- 0.07, moclobemide -0.52 +/- 0.09, selegiline -0.26 +/- 0.1. The mydriatic response to tyramine was potentiated by moclobemide, compared with the response recorded in the presence of placebo. The responses to tyramine (arbitrary units +/- s.e. mean) were: placebo 77.08 +/- 11.65, moclobemide 140.25 +/- 18.9, selegiline 72.75 +/- 12.35. Both moclobemide and selegiline significantly reduced platelet MAO activity, compared with placebo. The changes in platelet MAO activity (nmol h(-1) mg(-1) protein +/- s.e. mean) from the pretreatment level were: placebo 0.5 +/- 0.62, moclobemide -6.7 +/- 0.66, selegiline -17.7 +/- 0.87. Moclobemide significantly reduced plasma DHPG concentration, compared with placebo. The changes in plasma DHPG concentration (nmol l(-1) +/- s.e. mean) from the pretreatment level were: placebo -0.01 +/- 0.24, moclobemide -4.98 +/- 0.32, selegiline -0.51 +/- 0.26. CONCLUSIONS: The potentiation of tyramine-evoked mydriasis by moclobemide is likely to reflect the inhibition of MAO-A activity in the iris, consistent with the activity of this enzyme in sympathetic nerve terminals. The lack of effect of selegiline on tyramine-evoked mydriasis argues against a role of MAO-B in terminating the effects of sympathomimetic amines in the iris. The effects of the two drugs on platelet MAO activity and plasma DHPG concentration are in agreement with previous reports and consistent with the relative selectivity of moclobemide for MAO-A and of selegiline for MAO-B. The miosis caused by the two MAO inhibitors is likely to be due to a central sympatholytic action of the drugs.     

A study of transfer switching for the purpose of fault detection in FRIENDS

The authors have proposed a new concept of a distribution system “Flexible, Reliable and Intelligent ENergy Delivery System (FRIENDS)” with intent to solve imminent operating problems faced by utilities in providing their customers with reliable supply of power at several levels of quality. The main idea of FRIENDS is to introduce new facilities, so‐called Quality Control Centers (QCCs), which are installed very close to the customers for the purpose of implementing multiple functions, such as Customized Power Quality Service. In addition, these QCCs form a network for energy and information transmission at a level below distribution substations. QCCs make it possible to frequently change configuration of the network depending on the system and load conditions. These frequent reconfigurations of the network require fast and reliable Transfer Switching in the QCCs to ease an effect on customers. The reconfiguration for the purpose of fault area isolation also requires a fast Fault Detection feature. This paper presents a new method for controlling Transfer Switching and a method of Fault Detection in order to realize a fast and reliable reconfiguration of QCC network in a normal state, as well as under fault conditions. This paper also analyzes the methods in terms of instantaneous values calculated by PSCAD/EMTDC. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 148(3): 25–35, 2004; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10298     

New nibbled-page architecture for high-density DRAMs

A nibbled-page architecture which can be used to access all column addresses on the selected row address randomly in units of 8 bits at the 100 Mbit/s data rate is discussed. To realize such high-speed architecture, three key circuit techniques have been developed. An on-chip interleaved circuit has been used for the high-speed serial READ and WRITE operations. Column address prefetch and WE signal prefetch techniques have been introduced to eliminate idle time between 8 bit units. The nibbled-page architecture has been successfully implemented in an experimental 16 Mb DRAM, and 100 Mb/s operation has been achieved. The DRAM with nibbled-page mode is very effective in simplifying the design of high-speed data transfer systems     

Initial weight computation method with rapid convergence for adaptive array antennas

This paper presents a rapid initial weight computation method for adaptive array antennas. The proposed method estimates a correlation matrix and a correlation vector, where the correlation matrix is estimated using not only received samples with the desired signal, but also those before starting the transmission of the desired signal. The proposed method reduces the number of known symbols required for weight convergence. Furthermore, the combined use of the proposed method and the decision-feedback minimum mean square error combining method significantly improves weight convergence. Numerical results show that the combined method converges an array with sixteen antennas by using less than ten known symbols.     

Experimental study on the thermoelastic martensitic transformation in shape memory alloy polycrystal induced by combined external forces

Combined tension and torsion experiments with thin wall specimens of Cu-Al-Zn-Mn polycrystalline shape memory alloy (SMA) were performed at temperatureT =A _f + 25 K. The general stress-strain behaviors due to the thermoelastic martensitic transformation, induced by a combination of external forces of axial load and torque, were studied. It is shown that the progress of martensitic transformation (MT) at general stress conditions can be well considered as triggered and controlled by the supplied mechanical work (a kind of equivalent stress) in the first approximation. Pseudoelastic strains in proportional as well as nonproportional combined tension-torsion loadings were found fully reversible, provided that uniaxial strains were reversible. The axial strain can be controlled by the change of torque andvice versa due to the coupling among tension and torsion under stress, not only in forward transformation, but also in reverse transformation on unloading. The pseudoelastic strains of SMA polycrystal are path dependent but well reproducible along the same stress path. The evolution of macroscopic strain response of SMA polycrystal, subjected to the nonproportional pseudoelastic loading cycles with imposed stress path, was systematically investigated. The results bring qualitatively new information about the progress of the MT in SMA polycrystal, subjected to the general variations of external stress. PETR SITTNER, Research Associate, formerly with the Faculty of Engineering, Mie University     

Development of XLPE insulated DC cable

This paper describes the development of dc XLPE cable. Through a series of material investigations, an XLPE compound containing highly purified special filler was developed. To check the dc insulation performance of the cable insulated with this new material, a prototype cable with 9 mm insulation thickness was manufactured. It was confirmed that the performance of the prototype cable was excellent. Based on the study of the prototype cable, a 250-kV dc cable with 20 mm insulation thickness was designed and manufactured. Through a series of voltage tests, excellent dc insulation performance of the developed cable was verified.