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51.
This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.  相似文献   
52.
A psaC deletion mutant of the unicellular cyanobacterium Synechocystis sp. PCC 6803 was utilized to incorporate site-specific amino acid substitutions in the cysteine residues that ligate the FA and FB iron-sulfur clusters in Photosystem I (PS I). Cysteines 14 and 51 of PsaC were changed to aspartic acid (C14DPsaC, C51DPsaC, C14D/C51DPsaC), serine (C14SPsaC, C51SPsaC), and alanine (C14APsaC, C51APsaC), and the properties of FA and FB were characterized by electron paramagnetic resonance spectroscopy and time-resolved optical spectroscopy. The C14DPsaC-PS I and C14SPsaC-PS I complexes showed high levels of photoreduction of FA with g values of 2.045, 1. 944, and 1.852 after illumination at 15 K, but there was no evidence of reduced FB in the g = 2 region. The C51DPsaC-PS I and C51SPsaC-PS I complexes showed low levels of photoreduction of FB with g values of 2.067, 1.931, and 1.881 after illumination at 15 K, but there was no evidence of reduced FA in the g = 2 region. The presence of FB was inferred in C14DPsaC-PS I and C14SPsaC-PS I, and the presence of FA was inferred in C51DPsaC-PS I and C51SPsaC-PS I by magnetic interaction in the photoaccumulated spectra and by the equal spin concentration of the irreversible P700(+) cation generated by illumination at 77 K. Flash-induced optical absorbance changes at 298 K in the presence of a fast electron donor indicate that two electron acceptors function after FX in the four mutant PS I complexes at room temperature. These data suggest that a mixed-ligand [4Fe-4S] cluster is present in the mutant sites of C14X-PS I and C51X-PS I (where X = D or S), but that the proposed spin state of S = 3/2 renders the resonances undetectable in the g = 2 region. The C14APsaC-PS I, C51APsaC-PS I and C14D/C51DPsaC-PS I complexes show only the photoreduction of FX, consistent with the absence of PsaC. These results show that only those PsaC proteins that contain two [4Fe-4S] clusters are capable of assembling onto PS I cores in vivo.  相似文献   
53.
Sensitivity analysis of relative accommodation and vergence   总被引:1,自引:0,他引:1  
A sensitivity analysis was performed to determine the variation in response to changes in parameter values of a previously developed nonlinear static model of accommodation and vergence. To determine normal behavior, model simulation responses were computed using previously obtained parameter values in 4 subjects under 2 conditions. In the first, relative accommodation was evaluated by maintaining the vergence stimulus constant at 2.5 meter angles (MA) and varying the accommodative stimulus from -2.5 to 2.5 diopters (D) in 0.25-D steps. In the second, relative vergence was evaluated by maintaining the accommodative stimulus constant at 2.5 D and varying the vergence stimulus from 25 prism diopters (PD) base-in to 25 PD base-out in 5-PD steps. Sensitivity of the model parameters, consisting of controller gains for accommodation (ACG) and vergence (VCG), crosslink gains for accommodation-to-vergence (AC) and vergence-to-accommodation (CA), deadspace operators for accommodation (AE±AD) and vergence (VE±VD), and the tonic levels for accommodation (ABIAS) and vergence (VBIAS) were assessed by varying them at 50% and 150% of their normal values. It was found that the accommodation and vergence systems mere most sensitive to variation in crosslink gain, moderately sensitive to variation in controller gain and tonic level, and least sensitive to variation in size of the deadspace. These results may provide a quantitative basis for the occurrence of ocular dysfunctions associated with abnormal crosslink gains, such as strabismus, in clinical patients  相似文献   
54.
55.
The present study was performed to examine the central effects of antidepressants on nociceptive jaw opening reflex after intracisternal injection. we also investigated the mechanisms of central antinociceptive action of intracisternal antidepressants. We recorded the jaw opening reflex in freely moving rats and chose to administer antidepressants intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the spinal site of action of antidepressants. After intracisternal injection of 15 microg imipramine, digastric electromyogram (dEMG) was decreased to 76+/-6% of the control. Intracisternal administration of 30 microg desipramine, nortriptyline or imipramine suppressed dEMG remarkably to 48+/-2, 27+/-8, or 25+/-5% of the control, respectively. The suppression of dEMG was maintained for 50 min. L-NG-Nitroarginine methyl ester (NAME) blocked the suppression of dEMG from 32+/-2 to 81+/-5% of the control. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. The central NO pathway seems to be involved in the antinociception of intracisternal antidepressants at supraspinal sites.  相似文献   
56.
57.
BACKGROUND: Although transmission of hepatitis C virus (HCV) through parental exposure is well documented, it is still controversial whether familial clustering of HCV occurs. METHODS: To investigate risk factors for HCV infection, 109 cases and 84 non-infected controls were studied. In addition, 250 family members (104 men, 146 women) of cases and 170 family members of controls (64 men, 106 women) were tested for HCV infection using an anti-HCV antibody, alanine aminotransferase (ALT), and reverse transcribed polymerase chain reaction (RT-PCR). RESULTS: In the case-control analysis, people aged > or =60 were almost three times more likely to be infected by HCV than those aged <40. Risk of HCV infection was most strongly related to a history of blood transfusion (OR = 12.6, 95% CI: 4.3-36.5) followed by a history of jaundice (OR = 4.1, 95% CI: 1.3-12.6). Only one family member of cases and no-one related to the controls had HCV infection. CONCLUSIONS: These results suggest that, in Korea, age and parenteral exposure, such as a blood transfusion, are risk factors for HCV infection and familial clustering of HCV infection, if it occurs, is rare.  相似文献   
58.
OBJECTIVE: The study aimed to determine the effectiveness of prophylactic medical intervention in reducing the incidence of cystoid macular edema (CME) and the effectiveness of medical treatment for chronic CME after cataract surgery. DESIGN: The study design was a systematic review and meta-analysis of published reports of randomized clinical trials (RCTs). PARTICIPANTS: Sixteen RCTs involving 2898 eyes examining the effectiveness of medical prophylaxis of CME and 4 RCTs involving 187 eyes testing the effectiveness of medical treatment of chronic CME were used in the study. INTERVENTIONS: Medical prophylaxis of treatment (cyclo-oxygenase inhibitors or corticosteroids) versus control (placebo or active treatment) was performed. MAIN OUTCOME MEASURES: Incidence of angiographically diagnosed CME, incidence of clinically significant CME, and vision were measured. RESULTS: Thirty-six articles reported testing a prophylactic medical intervention for CME after cataract surgery. The incidence of CME varied extensively across studies and was related to the study design used. Summary odds ratios (OR) indicated that prophylactic intervention was effective in reducing the incidence of both angiographic CME (OR = 0.36; 95% confidence interval [CI] = 0.28-0.45) and clinically relevant CME (OR = 0.49; 95% CI = 0.33-0.73). There also was a statistically significant positive effect on improving vision (OR = 1.97; 95% CI = 1.14-3.41). A combination of the results of the four RCTs testing medical therapy for chronic CME indicated a treatment benefit in terms of improving final visual acuity by two or more Snellen lines (OR = 2.67; 95% CI = 1.35-5.30). Assessment of the quality of the 20 RCTs included in the meta-analyses indicated problems in the design, execution, and reporting of a number of trials. CONCLUSION: A combination of the results from RCTs indicates that medical prophylaxis for aphakic and pseudophakic CME and medical treatment for chronic CME are beneficial. Because most of the RCTs performed to date have problems related to quality, a well-designed RCT is needed to confirm this result, using clinical CME and vision as outcomes.  相似文献   
59.
Kell and Kx are two quantitatively minor proteins from the human erythrocyte membrane which carry blood groups antigens and are thought to be a metalloprotease and a membrane transporter, respectively. In the red cell membrane, these proteins form a complex stabilized by disulfide bond(s). Phosphorylation status of these proteins was studied, in the presence or absence of effectors of several kinases, either on intact cells incubated with [32P]-orthophosphate or on ghosts incubated with [gamma-32P]ATP. Purification of Kell-Kx complex, by immunochromatography on an immobilized human monoclonal antibody of Kell blood group specificity allowed to establish that (i) neither protein is phosphorylated on tyrosine; (ii) the Kell protein is a putative substrate for Casein Kinase II (CKII) and Casein Kinase I (CKI) but not for protein kinase C (PKC), whereas Kx protein is phosphorylated by CKII and PKC but not by CKI; (iii) Protein Kinase A neither phosphorylates the Kell nor the Kx proteins.  相似文献   
60.
N-acetyltransferase (NAT) activity was determined by incubation of purified Enterobacter aerogenes enzyme with 2-aminofluorene (2-AF) as the substrate, followed by high pressure liquid chromatography assays. The NAT activity from E. aerogenes was 0.58 +/- 0.08 nmol/min/mg protein for 2-AF. The values of apparent K(m) and Vmax were 0.72 +/- 0.14 mM and 2.45 +/- 0.29 nmol/min/mg protein, respectively, for 2-AF. The optimal pH value for the enzyme activity was 7.5 for the 2-AF tested. The optimal temperature for enzyme activity was 37 degrees C for the 2-AF substrate. The molecular weight of NAT from E. aerogenes was 44.9 kD. Among a series of divalent cations and salts, Zn2+, Ca2+, and Fe2+ were demonstrated to be the most potent protease inhibitors, and only ethylenediaminetetraacetic acid significantly protected the NAT. Iodoacetamide, in contrast to other agents, markedly inhibited NAT.  相似文献   
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