Crosslinking of apolipoprotein E by products of lipid peroxidation

Apolipoprotein E (APOE) genotype and advancing aging are interacting ri sk factors in the expression of late onset and sporadic Alzheimer's Disease (AD). We tested the hypothesis that 2 products of lipid peroxidation, malondialdehyde (MDA) and 4 hydroxy-2-nonenal (HNE), covalently modify APOE and alter its metabolism. In vitro, both HNE and MDA crosslinked purified APOE3 and APOE4. HNE was a more potent crosslinker than MDA, and purified APO3 was more susceptible to crosslinking by HNE than was purified APOE4. In P19 neuroglial cultures, oxidative stress with lipid peroxidation led to increased intracellular accumulation of anti-HNE and anti-APOE immunoreactive proteins of approximately 50 kDa. Intercellular accumulation of the 50 kDa APOE-immunoreactive protein (APOE-50) was not prevented by cyclohexamide, suggesting formation by post-translational mechanisms. In CSF, a 50 kDa APOE-immunoreactive protein co-migrated with proteins most immunoreactive for HNE and MDA adducts, containing NaB3H4-reducible bonds. These proteins were in CSF from adult subjects (with or without dementia), and in AD patients homozygous for APOE3 or APOE4 alleles. These data suggest that HNE covalently crosslinks APOE in P19 neuroglial cultures to form a 50 kDa protein, and that similar modifications of APOE appear to occur in vivo.     

Cervical radiculopathies: comparison of surgical and EMG localization of single-root lesions

To identify the various electrodiagnostic (EDX) patterns of C-5, C-6, C-7, and C-8 cervical radiculopathy, we compared 50 cases of surgically proven solitary-root lesions with their preoperative EDX patterns. We excluded patients with polyradiculopathy, myelopathy, and previous surgery. We classified EDX studies as abnormal only by the needle electrode examination, and only by the demonstration of fibrillation potentials (either the positive sharp wave or the biphasic spike form). Seven patients (14%) had C-5 radiculopathy, nine (18%) had C-6, 28 (56%) C-7, and six (12%) C-8. With C-5, C-7, and C-8 radiculopathies, changes were relatively stereotyped, with involvement of the spinati,deltoid, biceps, and brachioradialis with C-5; the pronator teres, flexor carpi radialis, triceps, and anconeus with C-7; and the first dorsal interosseous, abductor digiti minimi, abductor pollicis brevis, flexor pollicis longus, and extensor indicis proprius with C-8. The root lesion with the most variable presentation was C-6--in half the patients, the findings were similar to C-5 radiculopathies, except that the pronator teres tended to be involved, whereas in the other half, the findings were identical to those with C-7 radiculopathies.     

Combined QRD-M and DFE detection technique for simple and efficient signal detection in MIMO-OFDM systems

An efficient MIMO signal detection technique with low complexity is presented for MIMO-OFDM systems. The proposed technique has a feature of combined QRD-M and DFE detection. In our detection technique with M transmit antennas, after QRD-M detection is executed for first T detection steps, DFE detection is executed for last M - T detection steps. This approach is simple and has low complexity, because the computations for QRD-M is limited by the newly adopted parameter T. From simulation results, the complexity of the proposed technique with 4 × 4 and T = 2 is reduced by 61% compared with that of the conventional QRD-M at the expense of about 0.7dB degradation of BER performance at BER=10⁻⁴. The simulations are executed in Ricean and Rayleigh channel models. And the simulation of proposed technique is executed by using estimated channel. Through the simulations, it is ascertained that the proposed detection can be used for Ricean and Rayleigh channel models as well as estimated channel.     

Collagen type VI gene expression in the skin of trisomy 21 fetuses

Using site-directed mutagenesis, changes of Tyr221 in plasminogen activator inhibitor-1 (PAI-1) have provided mutants with normal activity, but with increased stability. At physiological conditions, the transition of the PAI-1 mutants Tyr221His and Tyr221Ser to the latent form was significantly prolonged (half-lives 14.8 and 4.1 h, respectively) as compared to wild-type PAI-1 (2.0 h). Their half-lives, especially for the Tyr221Ser mutant, were even more prolonged in the presence of vitronectin (23.8 and 53.7 h, respectively). While wild-type PAI-1 was more stable at lower pH, the PAI-1 mutants Tyr221His and Tyr221Ser had stability optima at about pH 6.5, but displayed shorter half-lives at pH 5.5.     

Noncariogenic intense natural sweeteners

There is a definite relationship between the dietary consumption of sucrose and the incidence of dental caries. Noncaloric sucrose substitutes for use in the sweetening of foods, beverages, and medicines may be either synthetic compounds or natural products. In the United States, four potently sweet artificial sweeteners are approved, namely, saccharin, aspartame, acesulfame potassium, and sucralose. Highly sweet plant constituents are used in Japan and some other countries, including the diterpene glycoside stevioside and the protein thaumatin. Recent progress in a research project oriented towards the discovery and evaluation of novel potentially noncariogenic sweeteners from plants has focused on substances in the sesquiterpenoid, diterpenoid, triterpenoid, steroidal saponin, and proanthocyanidin structural classes. The feasibility of using Mongolian gerbil electrophysiological and behavioral assays to monitor the sweetness of plant extracts, chromatographic fractions, and pure isolates has been investigated. An in vivo cariogenicity study on the commercially available natural sweeteners stevioside and rebaudioside A has been carried out.     

Anti-AIDS agents. 33. Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues

Four isomeric methyl substituted DCK analogues (2-5) were asymmetrically synthesized from different starting materials. 3-Methyl, 4-methyl, and 5-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (2-4) all were extremely potent against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of < 4.23 x 10(-7) microM and > 3.72 x 10(8), respectively, which are much better than those of DCK and AZT in this assay.