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This overview describes recent advances in molecular biology of neuronal ceroid lipofuscinoses (CLN). Despite intensive research during last 20 years, the basic defects of these autosomal recessive-progressive encephalopathies of childhood remain unknown. Consequently, no specific cure is available. Methods of positional cloning (reverse genetics) starting from random linkage approach have been applied to search for gene defects in the infantile and juvenile forms of the disease. The results of this random search for disease loci have for the first time revealed molecular heterogeneity of CLN diseases. The gene defect causing the infantile form has been assigned to 1p32 in the Finnish family material, whereas the disease locus of the juvenile form has been localized to 16p12 in European and Canadian families. Finally, the gene defect causing the late infantile form has been excluded from both 1p32 and 16p12 chromosomal regions, referring to a third, still unknown locus causing CLN disease. Consequently, reliable prenatal and carrier diagnostics have now become possible in families with the infantile and juvenile forms of the disease, and DNA-based prenatal diagnostics have been successfully applied in the infantile form. Most importantly, the assignment of gene loci has brought these fatal brain diseases within the reach of molecular cloning strategies that eventually will result in revealing both the infantile and juvenile CLN genes and in identifying corresponding gene products.  相似文献   
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We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping).  相似文献   
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DNA "fingerprint" (DNA-F) analysis, based on the polymorphism caused by numeric variations in the tandem repeats of minisatellite areas of the human genome, has a potential capacity to reveal even minor genomic changes. In this study we have applied DNA-F to the detection of residual disease in leukemia. In order to identify normal and leukemic cell populations, we used two molecular probes: Jeffrey's minisatellite probes and M13 wild type phage probe, which detect different sets of polymorphic fragments in the human genome. Comparison of varying minisatellite fragments between remission and relapse was performed by Southern blot hybridization in seven patients with acute lymphoblastic leukemia (ALL). The results suggest that Southern hybridization with DNA "fingerprint" probes can prove to be a sensitive method in the detection of minimal residual disease in ALL.  相似文献   
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Menstrual cycle and appetite control: implications for weight regulation   总被引:1,自引:0,他引:1  
Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.   相似文献   
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We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.  相似文献   
19.
Prenatal diagnosis was performed in 81 cases at risk for the fragile X syndrome. There were 12 fra(X)-positive cases, two of which showed low expression in cultured amniotic fluid cells. FUdR and high thymidine were used for induction of fra(X) (q27.3) expression in all cases. In 21 cases linkage studies were performed, 7 with probes for the loci DXS52, DXS98 and DXS105, 13 with probes for DXS369 and DXS296, DXS304 or DXS374 and one with the probe Do33 for DXS465. In 11 of these cases linkage analysis gave risk figures higher than 95% or lower than 5%, all in concordance with the cytogenetic findings. Discordance was found in three cases studied earlier, the two cases with low expression mentioned above and one cytogenetically normal case, which were now restudied with the new probes. RFLP-studies and linkage analysis was also performed for 24 cytogenetically fra(X)-negative females having a 50%, 25% or 12.5% risk of being carriers according to pedigree data. In 15 cases the risk dropped to 1% or less. Six of these women were pregnant and had asked for prenatal diagnosis but after genetic counseling prenatal diagnosis was avoided.  相似文献   
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Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.   相似文献   
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