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41.
Day DJ; Speiser PW; Schulze E; Bettendorf M; Fitness J; Barany F; White PC 《Human molecular genetics》1996,5(12):2039-2048
Steroid 21-hydroxylase deficiency is among the most common inborn errors of
metabolism in man. Characterization of mutations in the 21- hydroxylase
gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase
chain reaction (PCR). The most common mutation is conversion of an A or C
at nt656 to a G in the second intron causing aberrant splicing of mRNA.
Homozygosity for nt656G is associated with profoundly deficient adrenal
cortisol and aldosterone synthesis, secondary hypersecretion of adrenal
androgens, and a severe form of congenital adrenal hyperplasia (CAH)
characterized by ambiguous genitalia and/or sodium wasting in newborns.
During the course of genetic analysis of CYP21 mutations in CAH families,
we and others have noticed a number of relatives genotyped as nt656G
homozygotes, yet showing no clinical signs of disease. A number of lines of
evidence have led us to propose that the putative asymptomatic nt656G/G
individuals are incorrectly typed due to dropout of one haplotype during
PCR amplification of CYP21. For prenatal diagnosis, we recommend that
microsatellite typing be used as a supplement to CYP21 genotyping in order
to resolve ambiguities at nt656.
相似文献
42.
43.
B R Broxup V E Valli G L Losos D H Percy E Farber I McMillan 《Toxicologic pathology》1988,16(4):401-417
Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies. 相似文献
44.
The development of both adenocarcinoma of the jejunum and in situ squamous carcinoma of the oesophagus in an adult coeliac patient is described. Good evidence that adenocarcinoma of jejunum occurs more frequently in patients with coeliac disease has recently become available though this association has been suggested for some time. While oesophageal carcinoma has long been associated with coeliac disease, in situ carcinoma of oesophagus has not been previously described in these circumstances. We feel that the risk of this complication, as calculated from published series, warrants a screening programme for oesophageal malignancy in adult coeliacs. 相似文献
45.
46.
Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease 总被引:5,自引:2,他引:5
The allelic frequency of the gene for the K variant of
butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age
> 65 years) histopathologically diagnosed Alzheimer's disease (AD),
which was higher than the frequencies in 104 elderly control subjects
(0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed
cases of other dementia (0.10). The association of BCHE-K with late-onset
AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E
gene (APOE), among whom the presence of BCHE-K gave an odds ratio of
confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years
and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers
over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset
AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on
chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene
for late-onset AD.
相似文献
47.
48.
A 50-kDa membrane protein mediates sialic acid-independent binding and infection of conjunctival cells by adenovirus type 37 总被引:6,自引:0,他引:6
The ocular tropism of adenovirus type 37 (Ad37) does not correlate with the wide distribution of the 46-kDa coxsackievirus and adenovirus receptor (CAR), the major receptor for most adenovirus serotypes. We previously found that Ad37 infects and binds well to conjunctival cells (Chang C), but poorly to lung epithelial (A549) cells that express CAR and hypothesized that this serotype uses a distinct receptor that is selectively expressed on conjunctival cells. To test this, we produced particles of a fiber-deleted Ad5 vector containing the Ad37 fiber protein. The "pseudotyped" vector infected Chang C cells better than A549 cells using a CAR-independent pathway. Ad37 binding was calcium-dependent and was abolished by protease digestion of cell surface proteins. Using a virus overlay protein blot assay (VOPBA), we detected calcium-dependent Ad37 binding to 50- and 60-kDa membrane proteins on permissive Chang C cells. In contrast, calcium-dependent binding was detected with only the 60-kDa protein on nonpermissive A549 cells. Ad19p, a closely related serotype that failed to bind to conjunctival cells, recognized the 60-kDa, but not the 50-kDa, protein. Ad37 has been reported to use sialic acid instead of CAR as a cell receptor on A549 cells. Pretreatment of Chang C cells with neuraminidase abolished Ad37 binding to only the 60-kDa protein, suggesting that sialic acid mediates Ad37 binding to the 60-kDa protein. The pseudotyped Ad37 vector was also able to infect neuraminidase-treated Chang C cells. Thus, subgroup D adenoviral binding to the 50-kDa protein is calcium-dependent and cell type- and serotype-specific, whereas binding to the 60-kDa protein is not necessary for infection of conjunctival cells. Together, these data suggest that the 50-kDa protein is the major receptor for Ad37 on conjunctival cells. 相似文献
49.
50.
GD Cramer DJ Allen LJA DiDio W Potvin R Brinker 《Surgical and radiologic anatomy : SRA》1990,12(4):287-290
Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.
Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains
Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm3, mais il est chez les sujets masculins de 16,3 cm3 et chez les sujets de sexe féminin de 18 cm3. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.相似文献