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71.
Presymptomatic diagnosis in Portuguese FAP families using intragenic RFLPs and (CA)n flanking markers by fluorescence based semiautomated DNA analysis. 下载免费PDF全文
R Almeida P Fidalgo E Ramalho A Brás N Leit?o C Mira J Rueff C Monteiro 《Journal of medical genetics》1996,33(3):244-247
Owing to the large size of the APC gene, responsible for familial adenomatous polyposis, direct screening for individual mutations is not a practical approach. In the present study we establish the methodology of fluorescence based semi-automated DNA analysis to perform presymptomatic diagnosis of members at risk from 11 Portuguese FAP families with three (CA)n markers flanking the APC gene, MBC, CB26, and YN5.64, and four intragenic RFLPs. Haplotypes were constructed on the basis of individual genotypes and their segregation through generations were followed. The study was informative for 12% of subjects using only intragenic RFLPs and increased to 90% when we used the three (CA)n flanking markers. We report two of the 11 families under study in our laboratory and show recombinant events leading to a precise localisation of the CB26 marker between D5S82 and the APC gene. In one family there was a loss of (CA) units of one allele of the CB26 marker from an unaffected mother to her son. 相似文献
72.
Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up study of one extended family. 下载免费PDF全文
C E de Die-Smulders C J H?weler J F Mirandolle H G Brunner V Hovers H Brüggenwirth H J Smeets J P Geraedts 《Journal of medical genetics》1994,31(8):595-601
We have re-examined an extended myotonic dystrophy (DM) family, previously described in 1955, in order to study the long term effects of anticipation in DM and in particular the implications for families affected by this disease. This follow up study provides data on 35 gene carriers and 46 asymptomatic at risk family members in five generations. Clinical anticipation, defined as the cascade of mild, adult, childhood, or congenital disease in subsequent generations, appeared to be a relentless process, occurring in all affected branches of the family. The cascade was found to proceed asynchronously in the different branches, mainly because of an unequal number of generations with mild disease. The transition from the mild to the adult type was associated with transmission through a male parent. Stable transmission of the asymptomatic/mild phenotype showed a female transmission bias. We further examined the extent and causes of gene loss in this pedigree. Gene loss in the patient group was complete, owing to infertility of the male patients with adult onset disease and the fact that mentally retarded patients did not procreate. Out of the 46 at risk subjects in the two youngest generations, only one was found to have a full mutation. This is the only subject who may transmit the gene to the sixth generation. No protomutation carriers were found in the fourth and fifth generations. Therefore it is highly probable that the DM gene will be eliminated from this pedigree within one generation. The high population frequency of DM can at present not be explained by the contribution of asymptomatic cases in the younger generations of known families, but is probably caused by the events in the ancestral generations. 相似文献
73.
Sex ratio of the mutation frequencies in haemophilia A: coagulation assays and RFLP analysis. 下载免费PDF全文
A H Br?cker-Vriends F R Rosendaal J C van Houwelingen E Bakker G J van Ommen J J van de Kamp E Bri?t 《Journal of medical genetics》1991,28(10):672-680
Coagulation and RFLP data from 41 families with an isolated haemophilia A patient were used to estimate the sex ratio of mutation frequencies (nu/mu). Based on the results of coagulation assays in all the female relatives investigated, nu/mu was estimated to be 12.1 by the maximum likelihood method (95% confidence interval 3.8 to 62.5). In order to avoid the possible influence of germline mosaicism, an additional analysis was performed in which only the results in the mothers and grandmothers of an isolated patient were included. The nu/mu ratio was then estimated to be 5.2 (95% confidence interval 1.8 to 15.1). Because an estimate of nu/mu based on all available RFLP data can easily be biased in favour of males, we set up a model in which only information on the grandparental derivation of the patient's X chromosome was used, irrespective of the generation in which the mutation actually occurred. In this way nu/mu was estimated to be minimally 4. The probability of carriership for mothers of an isolated haemophilia A patient amounts to 86% with a sex ratio of 5.2. Although this would imply that 14% of the mothers are not carriers of the disease in the classical sense, they may be mosaic for the mutation and, therefore, also at risk of transmitting the mutation more than once. 相似文献
74.
Five modern bicycle helmets were studied to elucidate some of the variations in ventilation performance, using both a heated manikin headform and human subjects (n=7). Wind speed and head angle were varied to test their influence on the measured steady-state heat exchange (cooling power) in the skull section of the headform. The cooling power transmitted by the helmets varied from about 60% to over 90% of that of the nude headform, illustrating the range of present manufacturer designs. Angling the head forward by 30° was found to provide better cooling power to the skull (up to 25%) for three of the helmets and almost equal cooling power in the remaining two cases. Comparisons of skull ventilation at these angles with human subjects strongly supported the headform results. 相似文献
75.
Recent observations suggest that glutamate is important in sensory transduction in the periphery, contributing to peripheral sensitization of nociceptors and the hyperalgesia that accompanies inflammation. This study examined the presence of ionotropic glutamate receptors N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA) and kainate (KA) in normal human hairy skin (n=6) using immunohistochemistry at the electron microscopic level. Analysis of labeled axons at the dermal-epidermal junction demonstrated that 26. 9+/-2, 19.5+/-3 and 18.5+/-1% of the axons analyzed were labeled for subunits of the NMDA, AMPA or KA receptors, respectively. An occasional Schwann cell process was labeled for either NMDA or KA receptors. The findings support the hypothesis that glutamate and its ionotropic receptors may play a role in the periphery in sensory processing in humans. 相似文献
76.
Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells 总被引:8,自引:0,他引:8 下载免费PDF全文
77.
78.
Helmut Brunner Werner Schaeg Ursula Brück Ulrich Schummer Hans-Gerd Schiefer 《Medical microbiology and immunology》1977,163(1):25-35
A radioimmunoassay (RIA) which depends on the property of protein A ofStaphylococcus aureus to combine with the Fc-fragment of immunoglobulins was developed.This technique was employed to measure antibodies in human and various animal sera. It could be demonstrated that the staphylococcal RIA was at least as sensitive as the previously described radioimmunoprecipitation technique in detecting antibodies toM.pneumoniae in human sera. In addition, antibodies toM.pneumoniae could be demonstrated in sera of hamsters intranasally inoculated with the organisms. Antibodies could also be demonstrated in rabbit sera after immunization withM.pneumoniae. The test proved to be considerably more sensitive than conventional tests for detection of antibodies to the organisms. The test requires only small amounts of reagents and is relatively inexpensive.The results were presented in a preliminary form at the annual meeting of the Local Branch of the American Society for Microbiology, Frankfurt, March 1976 and the 77th ordinary meeting of the Society for General Microbiology, Glasgow, September 1976 相似文献
79.
Gropp E Shanabrough M Borok E Xu AW Janoschek R Buch T Plum L Balthasar N Hampel B Waisman A Barsh GS Horvath TL Brüning JC 《Nature neuroscience》2005,8(10):1289-1291
Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis. 相似文献
80.
Summary The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SHR) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study. 相似文献