Plasma levels of amyloid beta proteins Abeta1-40 and Abeta1-42(43) are elevated in Down''s syndrome

We report a case of pseudosarcomatous fibromyxoid tumor of the bladder in a 23-year-old man with a 2 month history of painless gross hematuria, which was studied by biphasic contrast-enhanced helical CT. CT demonstrated a 2 cm diameter polypoid enhancing mass in the anterior bladder wall. The lesion measured 103 and 91 HU on early and delayed images, respectively. Increased contrast enhancement was attributed to a histologically highly vascular myxoid stroma.     

Structural analysis of Alzheimer's beta(1-40) amyloid: protofilament assembly of tubular fibrils

Detailed structural studies of amyloid fibrils can elucidate the way in which their constituent polypeptides are folded and self-assemble, and exert their neurotoxic effects in Alzheimer's disease (AD). We have previously reported that when aqueous solutions of the N-terminal hydrophilic peptides of AD beta-amyloid (A beta) are gradually dried in a 2-Tesla magnetic field, they form highly oriented fibrils that are well suited to x-ray fiber diffraction. The longer, more physiologically relevant sequences such as A beta(1-40) have not been amenable to such analysis, owing to their strong propensity to polymerize and aggregate before orientation is achieved. In seeking an efficient and inexpensive method for rapid screening of conditions that could lead to improved orientation of fibrils assembled from the longer peptides, we report here that the birefringence of a small drop of peptide solution can supply information related to the cooperative packing of amyloid fibers and their capacity for magnetic orientation. The samples were examined by electron microscopy (negative and positive staining) and x-ray diffraction. Negative staining showed a mixture of straight and twisted fibers. The average width of both types was approximately 70 A, and the helical pitch of the latter was approximately 460 A. Cross sections of plastic-embedded samples showed a approximately 60-A-wide tubular structure. X-ray diffraction from these samples indicated a cross-beta fiber pattern, characterized by a strong meridional reflection at 4.74 A and a broad equatorial reflection at 8.9 A. Modeling studies suggested that tilted arrays of beta-strands constitute tubular, 30-A-diameter protofilaments, and that three to five of these protofilaments constitute the A beta fiber. This type of structure--a multimeric array of protofilaments organized as a tubular fibril--resembles that formed by the shorter A beta fragments (e.g., A beta(6-25), A beta(11-25), A beta(1-28)), suggesting a common structural motif in AD amyloid fibril organization.     

Alzheimer's peptides A beta 1-40 and A beta 1-28 inhibit the plasma cholesterol esterification rate

The amyloid fibrils of Alzheimer's disease and Down's syndrome amyloid deposits are composed mainly of aggregated amyloid beta protein (A beta) which also exists in a soluble form. It has been shown that both Alzheimer's disease and Down's syndrome share another common feature: the decrease in plasma cholesterol esterification in affected individuals. In the present work the effect of synthetic peptides A beta 1-40 and A beta 1-28 on normal human plasma cholesterol esterification rate was studied. Both peptides at a concentration of 1 ng/ml inhibited plasma cholesterol esterification rate to 40-50 % of control value. Statistical analysis showed no differences in the effect of A beta 1-40 and A beta 1-28 on the inhibition, suggesting the importance of A beta sequence 1-28 for this effect.     

镍(Ⅱ)、铜(Ⅱ)-5-Cl-PADAB-Tritonx-100体系显色反应的研究与应用

在pH =6 50的HAc -NH4 Ac缓冲介质中 ,在非离子型表面活性剂Tritonx -10 0存在下 ,镍 (Ⅱ )和铜 (Ⅱ )与 5-Cl-PADAB形成稳定的有色络合物。有色络合物最大吸收波长位于 52 0nm处 ,表观摩尔吸光系数分别为 4 7× 10 4 L/(mol·cm)和 4 6× 10 4L/(mol·cm) ,镍的质量浓度在 0～ 1 0 0mg/L ,铜的质量浓度在 0～ 1 12mg/L范围内符合比尔定律。该方法用于钢样中镍和铜的同时测定 ,获得满意结果     

Decreases in plasma A beta 1-40 levels with aging in non-demented elderly with ApoE-epsilon 4 allele

This report examines plasma amyloid beta proteins A beta 40 and A beta 42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-epsilon 4 allele (N = 94). A beta levels did not differ between the groups whereas the epsilon 4 allele was associated with a significant reduction in plasma apoE. In subjects with the epsilon 4 allele, increasing age was associated with significant reduction in plasma A beta 40. Subjects without the epsilon 4 allele showed a significant positive correlation between A beta 40 and A beta 42 levels. There was also a significant correlation between plasma A beta 40 and apoE levels in all subjects.     

Amyloid beta protein (A beta) deposition in dementia with Lewy bodies: predominance of A beta 42(43) and paucity of A beta 40 compared with sporadic Alzheimer''s disease

Few studies have evaluated computed tomography in glenohumeral osteoarthritis without humeral head elevation. Two recent studies included only ten and 11 patients, respectively. We evaluated computed tomography findings in 113 cases of primary glenohumeral osteoarthritis without humeral head elevation. Glenoid retroversion was substantially increased, with a mean of 16 degrees versus 8 degrees in a control group. The method used to measure this parameter was reproducible, with a mean interobserver variability of 4 degrees for a 95% confidence interval (P < or = 0.05). Humeral retrotorsion was apparently decreased (8 degrees), but osteoarthritis-related changes in the humeral head resulted in substantial measurement errors (interobserver variability, 11 degrees for a 95% confidence interval; P < or = 0.05). Humeral head subluxation was found in 35% of cases and measurement of this parameter was reproducible (interobserver variability, 4 degrees for a 95% confidence interval). Changes in the glenoid over time were dependent on the position of the humeral head in the glenoid fossa, which classified the shape of the glenoid with satisfactory reproducibility (intra- and interobserver Kappa, 0.68). The subscapularis and infraspinatus muscles were normal (stage 0 or 1) in 98% and 91% of cases, respectively and the method of Goutallier and Bernageau used for muscle evaluation proved highly reproducible (Kappa, 0.85). Computed tomography is invaluable for planning surgical treatment for primary glenohumeral osteoarthritis without humeral head elevation.     

(S)-(-)-[11C]nicotine binding assessed by PET: a dual tracer model evaluated in the rhesus monkey brain

PURPOSE: Determine the tissue distribution patterns for tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), gelatinase A and gelatinase B in normal and pathologic corneas. METHODS: Corneas were examined by immunohistochemistry, using antibodies to TIMP-1, TIMP-2, TIMP-3, gelatinase A or gelatinase B. RESULTS: In normal corneas, TIMP-1 antibody stained the epithelium and endothelium. TIMP-2 and TIMP-3 stained the epithelium, keratocytes and endothelium. Gelatinase A staining was weak and restricted to the epithelial cells. Radial keratotomy scars showed increased staining for TIMP-1 and TIMP-2 around the epithelial cell plug and along the incision. Bullous keratopathy corneas showed TIMP staining patterns similar to normal corneas and increased gelatinase A staining in regions of subepithelial fibrosis. Stromal scars of keratoconus corneas also had increased staining with TIMP-1 and TIMP-2 antibodies. In many keratoconus corneas, the TIMP-3 staining pattern was similar to normal corneas. However, in some keratoconus corneas, when Bowman's layer was missing, the stroma beneath was completely devoid of TIMP-3 antibody staining. No gelatinase B was seen in either the normal or diseased corneas. CONCLUSION: These data suggest that TIMP-1 and TIMP-2 are important for scar formation and corneal remodeling, since they were found in increased amounts at radial keratotomy incision sites and keratoconus scars. The significance of the focal stromal defects in TIMP-3 staining, associated with absence of Bowman's layer on keratoconus corneas, needs to be elucidated. At the stages of disease examined in this study, gelatinase B may not play a significant role in these pathological processes, since it was not seen in any of the corneas examined.     

(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).     

All-transglycolytic synthesis and characterization of sialyl(alpha2-3)galactosyl(beta1-4)xylosyl-p-nitrophenyl(beta1-), an oligosaccharide derivative related to glycosaminoglycan biosynthesis

Beta-D-Xylopyranosides, such as p-nitrophenyl-beta-D-xylopyranoside (Xyl-Np) or 4-methylumbelliferyl-beta-D-xylopyranoside (Xyl-MeUmb), when added to the culture medium of human skin fibroblasts have previously been shown to produce some Np- or MeUmb-oligosaccharides related to the regulation of glycosaminoglycan biosynthesis. Among these oligosaccharide derivatives, we synthesized the trisaccharide derivative NeuAc(alpha2-3)Gal(beta1-4)Xyl-Np(beta1- as a potential inhibitor of human skin fibroblast glycosaminoglycan biosynthesis. This synthesis was achieved by sequential use of transglycosylating activities of Escherichia coli beta-galactosidase and Trypanosoma cruzi trans-sialidase. The structure of the oligosaccharide obtained was determined by HPLC, ion-spray mass spectrometry, and NMR.     

Binding of a catechol derivative of denopamine (T-0509) and N-tert-butylnoradrenaline (Colterol) to beta 1- and beta 2-adrenoceptors

The affinities for beta-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N-tert-butylnoradrenaline; Col) were compared with those of other beta-agonists using a binding assay method. Specific binding of [3H]dihydroalprenolol (3H-DHA) to guinea pig left ventricular and lung membranes was saturable, and Scatchard and Hill analyses suggested that 3H-DHA bound to both membranes with a single population of binding sites with no binding site cooperativity. Addition of 5'-guanylylimidodiphosphate (GppNHp, 30 microM) led to a rightward shift of the 3H-DHA binding displacement curves of T-0509 and Col in both membranes, and the degree of shift was similar to that of full agonists such as isoproterenol (Iso), adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered to be full agonists at both beta 1- and beta 2-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both beta 1- and beta 2-adrenoceptors, and T-0509, like denopamine, was as selective for the beta 1-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the beta 2-subtype than Adr (4.5-fold compared with Iso).