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121.
Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availability of the genomic sequences of PMM2 allowed us to screen for mutations in 56 CDG1 patients from different geographic origins. By SSCP analysis and by sequencing, we identified 23 different missense mutations and 1 single-base-pair deletion. In total, mutations were found on 99% of the disease chromosomes in CDG1A patients. The R141H substitution is present on 43 of the 112 disease alleles. However, this mutation was never observed in the homozygous state, suggesting that homozygosity for these alterations is incompatible with life. On the other hand, patients were found homozygous for the D65Y and F119L mutations, which must therefore be mild mutations. One particular genotype, R141H/D188G, which is prevalent in Belgium and the Netherlands, is associated with a severe phenotype and a high mortality. Apart from this, there is only a limited relation between the genotype and the clinical phenotype. 相似文献
122.
A solid-state 2H NMR study of methyl-d3-cobalamin has been performed as a function of temperature to provide information concerning the character and energetics of the motion performed by this unique bioorganometallic methyl group. Analysis of the 2H NMR line shape indicates that the methyl group undergoes rapid three-fold rotation, and that the Co-C-2H angle lies between 105.9 and 109.5 degrees. Determination of the spin-lattice relaxation times T1 shows that the relaxation is anisotropic, consistent with a "jumping" motion of the methyl group rather than rotational diffusion. This also provides the activation energy to methyl jumps as 8.3 +/- 1.3 kJ/mol. It is proposed that this energetic barrier may be a useful probe of changes in the electronic character of the Co-C bond that accompany the biological role of this molecule in such enzymes as methionine synthase. 相似文献
123.
JR Mannino 《Canadian Metallurgical Quarterly》1998,98(10):542-546
The regular Papanicolaou (Pap) smear is cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high rate of false-negative results; therefore, serial examinations are necessary for optimal sensitivity. The sensitivity of the routine pelvic examination is further increased with the addition of colposcopy to cytologic screening. Patients identified as having disease by colposcopy and biopsy but not by Pap smear (false-negative), are followed up, and the progression of their disease is documented until the Pap smear reflects the known change. A total of 276 patients whose Pap tests showed "no abnormal cells" and mild dysplasia (CIN-1 [cervical intraepithelial neoplasia]) by colposcopy and biopsy, who opted not to be treated, were followed up as a function of time. The results of the Pap test on the 276 patients progressed to a low-grade squamous intraepithelial lesion (LGSIL) or higher within 42 months. In this study, false-negative Pap tests that were identified by simultaneously performed colposcopy became positive within 42 months; therefore, careful repetitive screening is necessary. The author argues that a definitive, prospective study on the addition of colposcopy or similar adjunct procedure to the routine pelvic examination, in selected cases, is needed. 相似文献
124.
J Rodríguez-Espinosa C Otal-Entraigas N Gascón-Roche J Mora-Brugués E Urgell-Rull JR Bordás-Serrat P Viscasillas-Molins 《Canadian Metallurgical Quarterly》1998,36(12):969-974
Mouse strains congenic for individual quantitative trait loci (QTLs) conferring hypnotic sensitivity to ethanol were constructed by backcrossing genotypically selected ILS x ISS N2 individuals to either inbred Long Sleep (ILS) or inbred Short Sleep (ISS) mice. We used a novel "speed congenic" approach in which N2 mice were genotyped for markers flanking each of the five originally identified QTLs. Genotypic selection for ISS regions at four of the five QTLs, and for ILS/ISS at the fifth QTL, allowed rapid fixation of the genetic background. We call this strategy "QTL-Marker-Assisted Counter Selection" or QMACS. By the N4 generation, phenotypic assessments showed that in some sublines the QTL had not been captured; these sublines were discarded and positive lines split to create new replicate sublines. One QTL, on Chromosome (Chr) 8, was not confirmed. At the N8, virtually all sublines on the remaining QTLs retained the phenotypic difference between heterozygotes and ISS homozygotes. Small numbers of interim congenics were produced at the N6 and later generations in which the ILS QTL was made homozygous on the ISS background; as expected, these congenic mice showed an increased sleep time. For later backcrosses (after the N4), the parents were selected on the basis of phenotype as well as genotype. The parent-offspring correlation over all QTLs was significant, supporting the use of phenotypic selection in congenic construction. 相似文献
125.
M Tahara JR Coorssen K Timmers PS Blank T Whalley R Scheller J Zimmerberg 《Canadian Metallurgical Quarterly》1998,273(50):33667-33673
The homotypic fusion of sea urchin egg cortical vesicles (CV) is a system in which to correlate the biochemistry and physiology of membrane fusion. Homologues of vesicle-associated membrane protein (VAMP), syntaxin, and SNAP-25 were identified in CV membranes. A VAMP and syntaxin immunoreactive band at a higher apparent molecular mass (approximately 70 kDa) was detected; extraction and analysis confirmed that the band contained VAMP, SNAP-25, and syntaxin. This complex was also identified by immunoprecipitation and by sucrose gradient analysis. VAMP in the complex was insensitive to proteolysis by tetanus toxin. All criteria identify the SNARE complex as that described in other secretory systems. Complexes exist pre-formed on individual CV membranes and form between contacting CV. Most notably, CV SNARE complexes are disrupted in response to [Ca2+]free that trigger maximal fusion. N-Ethylmaleimide, which blocks fusion at or before the Ca2+-triggering step, blocks complex disruption by Ca2+. However, disruption is not blocked by lysophosphatidylcholine, which transiently arrests a late stage of fusion. Since removal of lysophosphatidylcholine from Ca2+-treated CV is known to allow fusion, complex disruption occurs independently from the membrane fusion step. As Ca2+ disrupts rather than stabilizes the complex, the presumably coiled-coil SNARE interactions are not needed at the time of fusion. These findings rule out models of fusion in which SNARE complex formation goes to completion ("zippers-up") after Ca2+ binding removes a "fusion-clamp." 相似文献
126.
With the advent of the World Wide Web (WWW), we are now on the cusp of a revolution in computer technology that will dramatically enhance medical education. An historical analogy might be Johann Gutenberg's invention of movable type in the 1400's-radically decreasing the cost, time, and expertise required to reproduce printed materials. Now, the WWW can decrease the cost of disseminating medical educational materials. When an educational module is authored for the Web, it can be placed on a computer "server" which in turn, distributes the program on the WWW to anyone with a computer and Internet access. Rapidly emerging standards are being developed to allow increasingly rich educational experiences on the Internet. With the introduction of HTML (hypertext markup language), a standardized method of placing text and graphics, as well as the connections between them, was created. 相似文献
127.
Natural language data from 38 47-month-olds recorded at home in unstructured observations were analyzed and comparisons made of characteristics of mental state term use in child-friend, child-sibling, and child-mother dyads. Significantly more references to mental states were made by the children in conversations with siblings and friends than with mothers. Frequent use of mental state terms by both partners was related to cooperative interaction in both child-friend and child-sibling dyads and several associations were found with measures of language fluency, gender, and maternal education, although these varied across the 2 dyads. Children's use of mental state terms in conversations with siblings and friends was correlated with their performance on two false belief measures. Results highlight the importance of extending investigations into the social implications of the development of children's "theories of mind." 相似文献
128.
During a six-month period 2,221 haemocultures obtained from patients hospitalized in the Faculty Hospital Olomouc were examined. In all 304 isolated bacteria the sensitivity was assessed by the standard dilution micromethod and moreover all positive haemocultures were examined the "direct" disc method. Agreement between the results of the two methods was proved in 84% of pairs of tests and within a range from 67 to 100%, depending on the type of antimicrobial preparation. Based on these findings it may be stated that assessment of the sensitivity by the "direct" method agrees significantly with assessment of the sensitivity according to minimal inhibitory concentrations (MIC). In patients with septicaemia this procedure makes it possible to change empirical antibiotherapy by 24 hours sooner to aimed therapy. 相似文献
129.
Associations between coping responses, drinking motivations, expectations of meeting social and academic goals, and family of origin problem drinking and measures of college students' quantity/frequency of alcohol use and social complications of alcohol use were investigated in a sample of 218 college students. Positive associations were found between "emotion-focused" forms of coping such as detachment and the criterion measures, whereas "problem-focused coping" was not significantly associated with quantity/frequency of alcohol use or drinking complications. Positive correlations were also found between drinking motives, goal attainment expectancies and family models measures and the criterion measures. Regression models constructed for alcohol quantity/frequency and drinking complications implicated the total number of drinking motives, family models of problem drinking and the coping strategy of self-blame as strongly related to criterion measures. Positive social drinking motives and coping by seeking social support were implicated as possible protective factors. 相似文献
130.
Eighty subjects viewed and visually imagined upright or rotated alphanumeric characters and later judged whether test characters were previously seen or imagined (reality monitoring). Identification and test characters were presented verbally or visually. When characters were identified and tested verbally, source confusions (misjudging a seen character as "imagined" and vice-versa) were infrequent and were comparable for rotated and upright characters. When characters were identified and tested visually, source confusions were more frequent and were influenced by character rotation. Memories for imagined characters were especially susceptible to source confusion. Also source confusions for seen characters increased when characters were rotated. These results are consistent with the proposal that increasing sensory similarity between perceived and imagined items increases source confusion and that perceived rotation generates cognitive operations similar to those generated when the subject imagines a character rotated. 相似文献