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排序方式: 共有346条查询结果,搜索用时 20 毫秒
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Elomaa O Pulkkinen K Hannelius U Mikkola M Saarialho-Kere U Kere J 《Human molecular genetics》2001,10(9):953-962
Anhidrotic ectodermal dysplasia (EDA) is an X-linked disorder characterized by abnormal development of ectoderm and its appendices. The EDA gene encodes different isoforms of ectodysplasin, a transmembrane protein. The two longest isoforms, ectodysplasin-A1 and -A2, which differ by an insertion of two amino acids, are trimeric type II membrane proteins with an extracellular portion containing a short collagenous domain and a TNF ligand motif in the C-terminal region. We show that ectodysplasin is released from cells to the culture medium. Deletion constructs were used to localize the cleavage site and show that the putative recognition sequence of a furin-like enzyme is needed for the cleavage. Some EDA patients have missense mutations affecting this recognition sequence, suggesting that cleavage has biological significance in vivo. EDAR, a recently cloned member of the TNFR family and the product of the downless gene, is able to co-precipitate ectodysplasin, confirming that they form a ligand-receptor pair. In situ hybridization and immunostaining studies show that ectodysplasin and EDAR are expressed in adjacent or partially overlapping layers in the developing human skin. We conclude that as a soluble ligand, ectodysplasin is able to interact with EDAR and mediate signals needed for the development of ectodermal appendages. 相似文献
3.
Vendelin J Pulkkinen V Rehn M Pirskanen A Räisänen-Sokolowski A Laitinen A Laitinen LA Kere J Laitinen T 《American journal of respiratory cell and molecular biology》2005,33(3):262-270
We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth. 相似文献
4.
Location on chromosome 15 of the gene defect causing Marfan syndrome 总被引:22,自引:0,他引:22
K Kainulainen L Pulkkinen A Savolainen I Kaitila L Peltonen 《The New England journal of medicine》1990,323(14):935-939
BACKGROUND. Marfan syndrome, "the founding member" of the heritable disorders of connective tissue, is a common autosomal dominant disorder with highly variable clinical manifestations in the skeletal, ocular, and cardiovascular systems. The fundamental defect leading to this disease has escaped definition despite decades of research efforts by several groups of investigators. METHODS AND RESULTS. Using linkage analyses with polymorphic markers of the human genome, we mapped the genetic defect to chromosome 15 in five families with Marfan syndrome. With three polymorphic markers we obtained definitive proof of linkage in these families (lod score = 3.92, theta = 0.0 +/- 0.11). The most probable location of the gene for the disease is currently D15S45 (lod score = 3.32, theta = 0.0 +/- 0.12). CONCLUSIONS. The chromosomal localization of the mutation in Marfan syndrome is a first step toward the isolation and characterization of the defective gene and serves as a diagnostic test in families in which cosegregation of these markers with the disease has been confirmed. 相似文献
5.
The search for the mutations causing human diseases is reaching new gene areas with increasing speed with new cloned genes or polymorphic gene areas, being reported every week. The almost 300 cloned genes and over 1000 RFLP-loci of the human genome can be used as tools to approach most human gene defects. Once the linkage between the disease and the RFLP has been found, chromosomal "jumping" or pulsed field electrophoresis can be used to separate the DNA areas in the neighbourhood of the first found RFLP locus for more detailed studies and finally for the location of the defective gene. Once found, the detailed analysis of gene mutations still requires the use of several, technically very demanding approaches of molecular biology. New techniques, such as the multiplication of the required gene area in a test tube as well as RNase protection assays have been used successfully to pick out about 80-90% of the mutations which occur in one gene area and cause the disease of this gene area. The increased specificity and sensitivity of these modern approaches do not, however, necessarily lead to the rapid diagnosis of all inherited diseases. Even once a linkage has been established between RFLP locus and a disease the path is still a long one: as demonstrated in Duchenne's muscular dystrophy and Huntington's disease, we have diagnostic RFLP-linkages but the search for the gene defect continues. Further, the increased sensitivity of the mutation assays will eventually reveal all the variations in an individual.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Poor survival of cementless Biomet total hip: a report on 1,047 hips from the Finnish Arthroplasty Register 总被引:1,自引:0,他引:1
Puolakka TJ Pajamäki KJ Pulkkinen PO Nevalainen JK 《Acta orthopaedica Scandinavica》1999,70(5):425-429
In Finland, almost 50% of all hip replacements done after 1989 have been inserted without cement. Biomet components have been the most commonly used implants in cementless arthroplasties. Between 1985 and 1997, 4,300 prostheses were implanted because of primary osteoarthrosis. 4 different acetabular component designs have been identified as Biomet implants (Mallory-Head, Romanus, T-TAP, Universal) and were used in 1,047 hips. The 9-year survival of all arthroplasties using Biomet cups was only 65 (95% CI 61-69)% while that of arthroplasties using T-TAP-cups was only 58 (52-65)%. In contrast, the 7.5-year survival of arthroplasties using Romanus cups was 85 (79-91)%. The 98 (96-99)% 5-year survival of arthroplasties with Mallory-Head cups should be interpreted cautiously, since similar results of arthroplasties using the Universal cup with the same type of liner decline sharply to 93 (88-98)% only 1 year later. The poor survival of Biomet cementless prostheses in our series seems to be related to the poor survival of the cup. This finding was common to all metal shell designs using Hexloc liners. We recommend that Biomet cups with Hexloc liners should not be used and patients who have had them inserted should undergo regular clinical and radiographic follow-ups. 相似文献
7.
L. Pys A. Pulkkinen M. Korppi K. Remes K. Juntunen-Backman 《Pediatric pulmonology》1992,13(4):215-221
Sixty-seven atopy-prone children (atopic family group, AFG) and 52 children with no family history of atopy (NAFG) were followed for 10 years. During infancy, the mothers of the newborn AFG children were advised to adjust their infants' diet, with a view toward minimizing the risk of atopy, and not to keep pets. Pulmonary function tests, methacholine inhalation challenge (MIC), and skin prick tests (SPT) were done in order to evaluate the bronchial reactivity and skin reactivity in the two groups. A pathological result in MIC was found in 20 (30%) of the AFG children and in 10 (19%) of the NAFG children. Such results of MIC were more common in the children with positive SPT results than in those without (67% vs. 24%). In regard to the diet consumed in infancy, MIC was pathological in 23% of children with and in 36% without prophylactic diet in infancy. For MIC, using the new, Spira electro 2 dosimeter equipment, the sensitivity was 75% and specificity 97%, but the predictive value for diagnosing bronchial asthma was only 25%. The important advantage of our method is that the degree of bronchial reactivity can be estimated by responses to increasing provocative doses. Our observations confirm that the new method is suitable for detecting bronchial asthma in clinical practice but it seems not to be optimal for epidemiological studies. We concluded that later bronchial hyperreactivity can not be diminished by avoiding home pets or providing a hypoallergenic diet during infancy. 相似文献
8.
Maija Vaittinen Dorota Kaminska Pirjo K?kel? Matti Eskelinen Marjukka Kolehmainen Jussi Pihlajam?ki Matti Uusitupa Leena Pulkkinen 《Diabetes》2013,62(11):3747-3750
We have previously demonstrated that the expression of calcineurin-like phosphoesterase domain containing 1 (CPPED1) decreases in adipose tissue (AT) after weight reduction. However, the function of CPPED1 in AT is unknown. Therefore, we investigated whether the change in CPPED1 expression is connected to changes in adipocyte glucose metabolism. First, we confirmed that the expression of CPPED1 decreased after weight loss in subcutaneous AT. Second, the expression of CPPED1 did not change during adipocyte differentiation. Third, CPPED1 knockdown with small interfering RNA increased expression of genes involved in glucose metabolism (adiponectin, adiponectin receptor 1, and GLUT4) and improved insulin-stimulated glucose uptake. To conclude, CPPED1 is a novel molecule involved in AT biology, and CPPED1 is involved in glucose uptake in adipocytes.Lifestyle modification improves glucose metabolism and results in a substantial reduction in the risk of type 2 diabetes in the long-term (1). In searching new putative genes related to obesity and type 2 diabetes, we have previously demonstrated a multitude of changes in adipose tissue (AT) gene expression in response to weight reduction in individuals with metabolic syndrome (2,3). Among the downregulated genes was calcineurin-like phosphoesterase domain containing 1 (CPPED1) (2); its function in AT is completely unknown.Therefore, we continued to study the role of CPPED1 in AT in more detail. Interestingly, the experiment using a Simpson-Golabi-Behmel syndrome (SGBS) cell strain demonstrated an impact of CPPED1 small interfering RNA (siRNA) on insulin-stimulated glucose uptake in mature adipocytes. Overall, the results demonstrate that CPPED1 is a novel molecule expressed in AT and is related to adipocyte function. 相似文献
9.