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111.
Familial hypercholesterolaemia (FH) is a common inherited disorder, associated with premature vascular disease. FH may be caused by many different mutations in the low density lipoprotein receptor (LDLR) gene, about 700 mutations have been described, most of which occur rarely and often only in single families. Although particular mutations are prevalent in certain ethnic groups, countries with heterogeneous population bases (such as NZ) may carry a wide variety of mutations; making a gene screening approach the appropriate first step for a mutation detection programme. We have compared SSCP with DHPLC to assess their effectiveness as methods for LDLR mutation detection. Although five novel LDLR mutations were detected by SSCP in patients with FH, DHPLC was more sensitive, with eight novel mutations detected. Six of these mutations (T392M, R419G, Y421N, 1206-1207delCT, 1872delC, and 1943delC) were clustered in exons 9 and 13 of the EGF precursor homology domain, one (679-680delAC) in the ligand binding domain (exon 4) and the eighth (P774H) in the membrane-spanning domain (exon 16). Twenty five mutations were identified in 35 patients in total. Of these, we were able to detect only 64% of mutations by SSCP even though all variants were detected by DHPLC. All patients are heterozygous for the mutations, which is consistent with the clinical phenotypes. 相似文献
112.
We describe a simple method for computer quantification of eye movement (EM) potentials during REM sleep. This method can be applied by investigators using either period-amplitude (PA) or Fast Fourier Transform (FFT) spectral EEG analysis without special hardware or computer programming. It provides good correlations with visual ratings of EM in baseline sleep and after administration of GABAergic hypnotics. We present baseline data for both PA and FFT measures for 16 normal subjects, studied for 5 consecutive nights. Both visually rated and computer-measured EM density (EMD) showed high night-to-night correlations across baseline and drug nights and the computer measures detected the EMD suppression that is produced by GABAergic drugs. Measurement of EM in addition to stage REM provides biologically significant information and application of this simple computer method, which does not require pattern recognition algorithms or special hardware, could provide reliable data that can be compared across laboratories. 相似文献
113.
Summary A new stochastic model of the surface EMG is suggested and the spectral density of the surface EMG is studied theoretically and experimentally to confirm the validity of this model.Theoretical results show that while the contraction level is not so high, the shape of the spectral density (distribution) does not change and its amplitude is directly proportional to the motor unit firing frequency and recruitment.To illustrate the theoretical results, experiments were carried out for rectus femoris and biceps brachii. The surface EMG was lead off by bipolar surface electrodes. And the spectral density of the surface EMG was calculated using FFT algorithm.From these experimental results, it was confirmed that our theoretical results were almost valid. 相似文献
114.
Pumeechockchai W Bevitt D Agarwal K Petropoulou T Langer BC Belohradsky B Bassendine MF Toms GL 《Journal of medical virology》2002,68(3):335-342
The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence. 相似文献
115.
目的 探讨转染同源盒第7基因(HOXB7)siRNA质粒表达载体对人恶性黑色素瘤细胞株A375在裸鼠体内生长的影响.方法 裸鼠皮下接种人恶性黑色素瘤A375细胞,对2周后形成的瘤块进行分组干预.随机分为生理盐水对照组、阴性质粒组、HOXB7质粒组,观察转染后各组裸鼠移植瘤的生长情况;免疫组化法比较瘤体内微血管密度(MVD).结果 HOXB7质粒组的裸鼠移植瘤块生长慢、体积明显小于生理盐水对照组[(0.134±0.039)cm3比(1.006±0.235)cm3,P<0.05],而阴性质粒组瘤块体积大小与生理盐水对照组无统计学差异[(0.929±0.157)cm3比(1.006±0.235)cm3,P>0.05].HOXB7质粒组裸鼠体内肿瘤MVD低于生理盐水对照组[(2.8±1.9)比(19.9±5.6),P<0.05],阴性质粒组与生理盐水对照组无统计学差异[(18.1±5.5)比(19.9±5.6),P>0.05].结论 针对HOXB7 siRNA质粒表达载体可有效抑制A375细胞裸鼠体内肿瘤生长和瘤内血管生成. 相似文献
116.
Killmann R. Jaros G. G. Wach P. Graumann R. Moshage W. Renhardt M. Fleischmann R. H. 《Medical & biological engineering & computing》1995,33(5):643-651
A computer simulation study is performed to investigate the method of current density reconstruction to localise myocardial
ischaemia. A computer model of the entire human heart is used to simulate the excitation and repolarisation process in eight
topographically different cases of myocardial ischaemia. The associated magnetocardiogram is calculated at 37 positions of
the KRENIKON* biomagnetic measurement equipment. The method of current density reconstruction is applied at the S-point (the last discemible
deviation from the ST-segment at the end of the QRS-complex) of the MCG to find characteristics of the myocardial ischaemia
simulated by the model. The results show that it is possible to determine the location of the ischaemia. The current density
distribution may be interpreted physiologically in terms of the so-called ‘injury current’. This indicates that magnetocardiography
might be a suitable method for noninvasive ischaemia diagnosis, and further investigations of the current density reconstruction
method for the injury current should be performed on patients with ischaemic heart disease. 相似文献
117.
The specific aims of this study were to examine age differences in visual acuity among young adult (5 years), middle aged (12 years) and aged (22 years) rhesus monkeys in relation to foveal cone density in the diurnal duplex retina. Classically, acuity has been defined as the reciprocal of the least resolvable detail measured in minutes of visual angle. The minimum separable binocular acuity mean of the young adult group was 0.83 ± 0.11, middle age acuity mean was 0.86 ± 0.12, and the acuity mean of the aged monkeys was 2.0 – 0.70 minutes of visual angle. According to analysis of variance and multiple range tests for specific group means, the 0.83' acuity m mean of the young, and the 0.86' acuity mean of the middle age group did not differ significantly, whereas the 2.0' acuity mean of the old group differed significantly from the 2 younger age groups. Foveal cone density was determined morphometrically by assesmeent of cone inner segment width, and absolute cone inner segment number per 100 Am along the horizontal meridian of the pure cone, rod free 1° × 1° foveola. Foveal cone density decreased significantly from 44.16 per 100 Am in the middle age group to 39.00 per 100 Am in the old macaque group. Since the diurnal macaque is of the same taxonomic order as man, and the visual systems of the two species are directly comparable in terms of ac acuity and the central receptive field organization of the retino-geniculo-striate system, it may be concluded that the macaque may represent an attractive and valid model for studies of aging in photopic and scotopic vision of diurnal primates, including man. 相似文献
118.
Tessitore L Batetta B Vizio B Mulas MF Marengo B Dessi S 《International journal of experimental pathology》2000,81(4):241-248
Sexual dimorphism exists in the response of rats to lead nitrate, liver hyperplasia occuring earlier and being more pronounced in males. Excess dietary choline in females shifted the growth pattern towards that of males. To determine whether phosphatidylcholine-induced growth modulations could be related to a derangement of cholesterol metabolism, liver accumulation of cholesterol esters and plasma lipoprotein patterns were investigated. In males, lead-induced liver hyperplasia was associated with increased total cholesterol hepatic content, accumulated cholesterol esters and reduced concentration of plasma High Density Lipoprotein (HDL) cholesterol. Females were less responsive to the liver mitogenic signal of lead nitrate; there was no elevation of cholesterol content nor any marked accumulation of cholesterol esters. This is consistent with the lack of change in the plasma levels of HDL cholesterol. Continuous choline feeding displaced the liver cholesterol ester pattern and plasma HDL cholesterol levels in females, and in parallel that of DNA synthesis, towards those of males. Choline was not observed to have any effect in males. These results suggest that the derangement of phosphatidylcholine metabolism induces growth-related changes in cholesterol turnover; they are consistent with the proposal that the intracellular content of cholesterol esters may have a role in regulating liver growth rates. 相似文献
119.
Genetics of the low density lipoprotein receptor: 总被引:1,自引:0,他引:1
Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs. 相似文献
120.
Claes Lundsteen Beth Bjerregaard Erik Granum John Philip Kim Philip 《Clinical genetics》1980,17(3):183-190