Genome-Wide Association Study of Coronary Artery Disease

Coronary artery disease (CAD) is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS) on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD

Polar Antiferromagnets Produced with Orbital-Order

Polar magnetic states are realized in pseudocubic manganite thin films fabricated on high-index substrates, in which a Jahn-Teller (JT) distortion remains an active variable. Several types of orbital-orders were found to develop large optical second harmonic generation, signaling broken-inversion-symmetry distinct from their bulk forms and films on (100) substrates. The observed symmetry-lifting and first-principles calculation both indicate that the modified JT q2 mode drives Mn-site off-centering upon orbital order, leading to the possible cooperation of "Mn-site polarization" and magnetism.Comment: 5 pages, 4 figure

Noncovalent Modification Strategy with Achiral Phosphoric Acid Diesters for Designing a Chiral Brønsted Base Organocatalyst

A strategy for designing chiral Brønsted base organocatalysts through noncovalent modification of a chiral dibasic molecule with an achiral phosphoric acid diester is introduced for the first time. Such a molecular modification concept utilizing acid-base interactions may facilitate the on-demand design of asymmetric organocatalysts, as preliminarily demonstrated in this work

豊田法による無カテーテル尿管皮膚痩術の成績

最近9年間に, 43症例67尿管に対し豊田法により無カテーテル尿管皮膚瘻術を行った.対象患者は男性30例, 女性13例, 平均年齢は61.4歳で, そのほとんどが膀胱, 直腸, 前立腺, 子宮の悪性腫瘍であった.両側性の場合は, 原則として左右尿管を一ヵ所に出す二連銃式尿管皮膚吻合術(double barrel ureterostomy)を行った.術前術後の腎盂像の推移をIVPで追求できた60尿管についてみると, 単側性の場合は20尿管中4尿管を除けばほぼ満足すべき結果を得ている.Double barrel法40尿管について, stoma側では中等度以上の腎盂拡張が20尿管中3尿管であったが, stomaと反対側では腎機能に影響が出ることが多く, 20尿管中3尿管に中等度の腎盂拡張が, また5尿管に高度の腎盂拡張または腎機能喪失があった.術後間もなく汎血管内凝固症候群で死亡した1例を除き, 結果的にはstoma付近が強い炎症性肉芽に覆われた1例と尿管の狭窄を生じた2例を除いた42例中39例(92.8%)をtubelessの尿管皮膚瘻としえたTubeless cutaneous ureterostomy by Toyoda's method was conducted in 67 ureters from 43 patients during the last 9 years. Subjects included 30 males and 13 females, with an average age of 61.4 years. Most of them were afflicted with malignant tumors in the bladder, rectum, prostate, or uterus. For bilateral ureterostomy, the double-barrel method was performed in which the stoma was made at the same site in both the right and left ureters. Among 60 ureters in which pre- and postoperative changes in the renal pelvis could be traced by IVP, satisfactory results were obtained in 16 of 20 ureters treated by unilateral surgery. Of the 40 ureters treated by the double-barrel method, moderate or severe pyeloectasis was observed in 3 of the 20 ureters on the side of the stoma, while moderate pyeloectasis was seen in 3 of 20 ureters of the side opposite the stoma, and severe pyeloectasis or loss of renal function was noted in 5. Thus, renal function on the side opposite the stoma was frequently influenced by the procedure. A patient who died of disseminated intravascular coagulation syndrome soon after the operation was excluded from analysis. Tubeless cutaneous ureterostomy could be conducted in 39 of 42 patients (92.8%), excluding one whose stoma and its periphery were covered with severe inflammatory granulation and 2 with ureteral constriction

Early stages of development of rat brain tumors induced by JC virus: a sequential histological and immunohistochemical study.

In order to clarify the origin of JC virus-induced brain tumors in rats, the development of tumors was sequentially analyzed histologically and immunohistochemically. Twenty-two of 30 rats (73%), which were intracerebrally inoculated with JC virus within 24 h of birth (group 1), developed, as a group, 45 brain tumors after 12 to 26 weeks. Seventeen of 27 rats (63%), which were inoculated on the 7th day after birth (group 2), developed 37 brain tumors as a group after a time 12 to 40 weeks. The tumors were found exclusively in the cerebrum. The microtumors, which were defined as tumors less than 2 mm in diameter, were located in the subependymal plate around the ventricular system. The microtumors and most part of the macrotumors consisted of cells of undifferentiated neuroectodermal nature, showing nuclear palisades and Homer-Wright-pseudorosette-like structures. Some tumor cells of macrotumors had an astrocytic nature and were positive for glial fibrillary acidic protein, S-100, Leu 7, and vimentin. In conclusion, the target cells of JC virus in rats may be undifferentiated subependymal cells of the cerebrum. The tumor cells show partial glial differentiation as they grow.</p

Spearmint Extract Containing Rosmarinic Acid Suppresses Amyloid Fibril Formation of Proteins Associated with Dementia

Neurological dementias such as Alzheimer’s disease and Lewy body dementia are thought to be caused in part by the formation and deposition of characteristic insoluble fibrils of polypeptides such as amyloid beta (Aβ), Tau, and/or α-synuclein (αSyn). In this context, it is critical to suppress and remove such aggregates in order to prevent and/or delay the progression of dementia in these ailments. In this report, we investigated the effects of spearmint extract (SME) and rosmarinic acid (RA; the major component of SME) on the amyloid fibril formation reactions of αSyn, Aβ, and Tau proteins in vitro. SME or RA was added to soluble samples of each protein and the formation of fibrils was monitored by thioflavin T (ThioT) binding assays and transmission electron microscopy (TEM). We also evaluated whether preformed amyloid fibrils could be dissolved by the addition of RA. Our results reveal for the first time that SME and RA both suppress amyloid fibril formation, and that RA could disassemble preformed fibrils of αSyn, Aβ, and Tau into non-toxic species. Our results suggest that SME and RA may potentially suppress amyloid fibrils implicated in the progression of Alzheimer’s disease and Lewy body dementia in vivo, as well

Effect of branched-chain amino acid supplementation on the oxidized/reduced state of plasma albumin in rats with chronic liver disease

We examined whether continuous supplementation with branched-chain amino acids phosphorylates ribosomal protein S6, a downstream effector of mammalian target of rapamycin, and improves hypoalbuminemia of rats with chronic liver disease. Sprague-Dawley rats were fed a casein diet (control group) or a branched-chain amino acid-supplemented casein diet (branched-chain amino acid group) for 11 weeks with repeated injections of carbon tetrachloride. Throughout this experimental period, no significant difference in plasma albumin concentration was seen between groups. The percentage of reduced albumin within total plasma albumin gradually decreased in both control and branched-chain amino acid groups. After 11 weeks with supplementation, phosphorylation of ribosomal protein S6 was significantly increased in the liver of rats in the branched-chain amino acid group compared with the control group. Furthermore, the percentage of reduced albumin within total albumin was significantly higher in the branched-chain amino acid group than in the control group. These results indicate that continuous supplementation with branched-chain amino acids in rats with chronic liver disease induces phosphorylation of hepatic ribosomal protein S6 and attenuates decreases in the percentage of reduced albumin, although levels of plasma albumin are not increased

Effect of Surface Pre-Reacted Glass Ionomer Containing Dental Sealant on the Inhibition of Enamel Demineralization.

The effect of a surface pre-reacted glass ionomer (S-PRG)-containing sealant on the demineralization inhibition and remineralization of intact enamel adjacent to the sealant material was investigated. BeautiSealant (BTS, S-PRG sealant, Shofu), Teeth Mate F-12.0 (TMF, fluoride-releasing sealant, Kuraray Noritake Dental), and an experimental silica-filler sealant were investigated. After pH cycling for 10 days, the enamel surface adjacent to the sealant material was observed using confocal laser microscopy and scanning electron microscopy. The polymerized sealant disks were immersed in a demineralized solution (pH: 4.3) to measure pH change. The enamel specimens with polymerized sealant disks were additionally immersed in demineralized solution, followed by energy-dispersive X-ray spectroscopy. The demineralized area of BTS was significantly smaller than that of TMF and SS (p &lt; 0.05). The surfaces adjacent to the sealant of TMF and SS were demineralized, while the surface of BTS was comparatively intact. An increase in pH values were observed in the BTS and TMF groups. Enamel surfaces presented an inhibition of demineralization for BTS and TMF, but not for SS. Fluoride uptake from the polymerized sealant was greater for BTS than for TMF. The S-PRG-containing sealant showed a buffering ability, demineralization inhibition, promotion of remineralization, and it can be advised for clinical applications