Characterization of histopathology and gene-expression profiles of synovitis in early rheumatoid arthritis using targeted biopsy specimens

The disease category of early rheumatoid arthritis (RA) has been limited with respect to clinical criteria. Pathological manifestations of synovitis in patients whose disease is clinically classified as early RA seem to be heterogeneous, with regular variations. To clarify the relation between the molecular and histopathological features of the synovitis, we analyzed gene-expression profiles in the synovial lining tissues to correlate them with histopathological features. Synovial tissues were obtained from knee joints of 12 patients with early RA by targeted biopsy under arthroscopy. Surgical specimens of long-standing RA (from four patients) were examined as positive controls. Each histopathological parameter characteristic of rheumatoid synovitis in synovial tissues was scored under light microscopy. Total RNAs from synovial lining tissues were obtained from the specimens selected by laser capture microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase. Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels of gene expression in multilayered lining tissues, compared with those of normal-like lining tissues in specimens from the same person, were determined to estimate gene-expression profiles characteristic of the synovial proliferative lesions in each case. Based on cluster analysis of all cases, gene-expression profiles in the lesions in early RA fell into two groups. The groups had different expression levels of genes critical for proliferative inflammation, including those encoding cytokines, adhesion molecules, and extracellular matrices. One group resembled synovitis in long-standing RA and had high scores for some histopathological features – involving accumulations of lymphocytes and plasma cells – but not for other features. Possible differences in the histopathogenesis and prognosis of synovitis between the two groups are discussed in relation to the candidate genes and histopathology

Benzene substituted with bipyridine and terpyridine as electron-transporting materials for organic light-emitting devices

New electron-transporting materials for organic light-emitting devices (OLEDs) based on trisubstituted benzene with both bipyridine and terpyridine, 1,3-bisbipyridyl-5-terpyridylbenzene (BBTB) and 1-bipyridyl-3,5-bisterpyridylbenzene (BTBB), were developed. Glass transition temperatures of BBTB and BTBB were 93 degrees C and 108 degrees C, respectively, and BTBB was completely amorphous with no melting point. Electron mobilities of BTBB exceeded the order of 10(-4) cm(2) V-1 s(-1), while those of BBTB were very high and reached 10(-3) cm(2) V-1 s(-1) at an electric field of approximately 500 kV cm(-2). These high mobilities contributed to a low voltage operation. For example, in the case of the conventional aluminum trisquinolinol (Alq)-based fluorescent OLED with BTBB, current densities of 3.5 mA cm(-2) and 100 mA cm(-2) were reached at voltages of 3.0 V and 4.5 V, respectively. In addition, ionization potentials of BBTB (6.33 eV) and BTBB (6.50 eV) were sufficiently large to confine holes in common emissive layers.ArticleJOURNAL OF MATERIALS CHEMISTRY. 22(14):6765-6773 (2012)journal articl

Role of premature leptin surge in obesity resulting from intrauterine undernutrition

SummaryIntrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to “developmental origins of health and disease.

グラヤノトキシンD環の化学修飾

Grayanotoxin (GTX), one of the lipid-soluble Na+ channel openers, contains four rings (A, B, C and D) and the chemical groups essential for the pharmacological action are located on the A- and B-rings. To study the biological significance of functional groups on the D-ring, 51 new derivatives were prepared from α-dihydro GTX- 11 . These new compounds and the previously prepared GTXS ere directly applied to the intracellular phase of internally perfused squid giant axons

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex

Benzene substituted with bipyridine and terpyridine as electron-transporting materials for organic light-emitting devices

New electron-transporting materials for organic light-emitting devices (OLEDs) based on trisubstituted benzene with both bipyridine and terpyridine, 1,3-bisbipyridyl-5-terpyridylbenzene (BBTB) and 1-bipyridyl-3,5-bisterpyridylbenzene (BTBB), were developed. Glass transition temperatures of BBTB and BTBB were 93 degrees C and 108 degrees C, respectively, and BTBB was completely amorphous with no melting point. Electron mobilities of BTBB exceeded the order of 10(-4) cm(2) V-1 s(-1), while those of BBTB were very high and reached 10(-3) cm(2) V-1 s(-1) at an electric field of approximately 500 kV cm(-2). These high mobilities contributed to a low voltage operation. For example, in the case of the conventional aluminum trisquinolinol (Alq)-based fluorescent OLED with BTBB, current densities of 3.5 mA cm(-2) and 100 mA cm(-2) were reached at voltages of 3.0 V and 4.5 V, respectively. In addition, ionization potentials of BBTB (6.33 eV) and BTBB (6.50 eV) were sufficiently large to confine holes in common emissive layers.ArticleJOURNAL OF MATERIALS CHEMISTRY. 22(14):6765-6773 (2012)journal articl