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排序方式: 共有333条查询结果,搜索用时 46 毫秒
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Transgenic technology in farm animals--progress and perspectives 总被引:4,自引:0,他引:4
Wolf E Schernthaner W Zakhartchenko V Prelle K Stojkovic M Brem G 《Experimental physiology》2000,85(6):615-625
Current applications of gene transfer in farm animals include the improvement of product quality and quantity, disease resistance, the production of valuable proteins in the mammary gland or other organs, the genetic modification of pigs for xenotransplantation and the generation of new animal models in cases where rodent models are not sufficient for studying the problem under evaluation. Although DNA microinjection into pronuclei of zygotes from various farm animal species has happened since 1985, the efficiency of this method is low. Further drawbacks are related to the random integration process which may cause mosaicism, insertional mutations and varying expression due to position effects. Sperm-mediated gene transfer is not routinely established yet, although the mechanisms of binding and internalisation of DNA by sperm cells is becoming increasingly clearer. New protocols for the use of retroviral vectors to infect metaphase II oocytes which are subsequently fertilised resulted in efficient production of transgenic cattle. In spite of extensive efforts to establish pluripotent stem cells from farm animal species, no germ-line competent cells have been reported in mammalian species other than mouse so far. However, recent success in cloning sheep, cattle, goats and pigs from cultured cells provides an alternative route for efficient and targeted genetic modifications of farm animals. 相似文献
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Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q) 总被引:10,自引:0,他引:10
OBJECTIVE: To report a family with X-linked Charcot-Marie-Tooth disease (CMTX) with proven connexin 32 (Cx32) mutation associated with deafness. METHODS: Twelve members of a CMTX family were examined clinically. Electromyography and sensory and motor conduction studies were performed in three men, two women, and a 7-year-old boy. Audiometric testing was carried out in the three men, one woman, and an 8-year-old girl. Molecular genetic analysis was performed in six men and five women. RESULTS: The three men and the 7-year-old boy had the usual sensorimotor deficit and pronounced reduction of motor nerve conduction velocity. A 15-year-old boy was asymptomatic and had only areflexia. The women had impairment of vibratory sensation and slight slowing of nerve conduction velocities. Sensorineural deafness was observed in the three men and in an 8-year-old girl without any motor or sensory deficit. Molecular genetic analysis revealed a new missense mutation located in codon 142 of the Cx32 gene leading to the substitution of an arginine by a glutamine. CONCLUSION: CMTX due to Cx32 mutations often shows interfamilial and intrafamilial phenotypic variation, which is also the hallmark of this family. The sensorineural deafness observed in this family suggests that Cx32 could play an important role in the auditory pathway. 相似文献
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Breteau G Stojkovic T De Seze J Gauvrit J Pruvo J Vermersch P 《Revue neurologique》2000,156(8-9):786-789
We report two cases of viral myelitis, one associated with adenovirus and the other with Epstein-Barr virus. The clinical presentation and course were similar, with viral illness, paraplegia with a D4 sensory level, and fever. Spinal magnetic resonance imaging showed a T2 cervico-dorsal high intensity signal. Cerebrospinal fluid examination showed pleocytosis without oligoclonal bands. Both patients recovered after treatment with high-dose methylprednisolone.These two cases suggest a similar clinical and paraclinical pattern in viral transverse myelitis. Moreover, treatment with corticosteroids seems to be useful in viral myelitis. 相似文献
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Douay X de Seze J Stojkovic T Gauvrit JY Savage C Pruvo JP Vermersch P 《Revue neurologique》2000,156(6-7):661-664
A 38 year-old woman, without previous medical history, presented, since 1993, several paraplegic fits carrying herself progressively through to a severe paraplegia. Diagnoses successively proposed were spinal cord compressions by slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the patient presented back pain and fever. Spinal cord magnetic resonance imaging (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The lesions were isointense on T1-weighted images, hyperintense on T2-weighted images and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear), protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first treated with parenteral unspecific antibiotherapy. Microbiological studies of blood and CSF were negative. CSF examination with polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms and CSF abnormalities decreased after antituberculous treatment. However, paraparesis remain severe. Spinal tuberculous localizations often lead to diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and using of PCR technics in CSF would contribute to reduce these difficulties. 相似文献
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De Seze J Ayachi M Stojkovic T Gauvrit JY Saint Michel T Pruvo J Vermersch P 《Revue neurologique》2000,156(5):491-496
Spinal cord magnetic resonance imaging (MRI) is of particular interest in the management of multiple sclerosis (MS) especially in primary progressive forms. Most of the demyelinating lesions are located in the cervical or dorsal cord. Spinal cord area reduction has been recently correlated with the progression of disability (Losseff et al., 1996, Lycklama a Nijeholt et al., 1998). The aim of this study was to confirm this first result, to assess the reproducibility of this method and to correlate demyelinating lesions with spinal cord area reduction. Fifty two patients were included and compared with 15 controls (normal subjects). T2 Sagittal and axial plane images were performed to localized hypersignal lesions. Spinal cord area was obtained by a volume acquired inversion prepared fast spoiled gradient echo acquisition (MP-Rage) sequence. We compared the mean area value with clinical parameters (age, course of the disease, expanded disability status scale ?EDSS) and with the number and location of demyelinating lesions. Demyelinating lesions were found in 82p.100 of MS patients and in none of controls. Mean spinal cord area was closely similar to Losseff et al. (1996) results and was reduced compared with controls (p<0.001). Spinal cord reduction was correlated with disability, studied by the EDSS. Furthermore, no correlation was found between demyelinating lesions and spinal cord area reduction. This study confirms the interest of spinal cord area mesurement in MS. Spinal cord atrophy is a reliable marker for axonal loss. This method should be of particular interest for the follow-up of axonal loss in thepeutic trials especially in primary progressive MS. 相似文献
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Milica J. Nesic Biljana Stojkovic Nadja P. Maric 《Psychiatry and clinical neurosciences》2019,73(12):723-730
Considering the relatively high heritability of schizophrenia and the fact that it significantly reduces the reproductive fitness of affected individuals, it is not clear how the disorder is still maintained in human populations at a disproportionally high prevalence. Many theories propose that the disorder is a result of a trade‐off between costs and benefits of the evolution of exclusively human adaptations. There have also been suggestions that schizophrenia risk alleles are accompanied with increase in fitness of affected persons or their relatives in both past and current social contexts. The discoveries of novel schizophrenia‐related genes and the advancements in comparative genomics (especially comparisons of the human genome and the genomes of related species, such as chimpanzees and extinct hominids) have finally made certain evolutionary theories testable. In this paper, we review the current understanding of the genetics of schizophrenia, the basic principles of evolution that complement our understanding of the subject, and the latest genetic studies that examine long‐standing evolutionary theories of schizophrenia using novel methodologies and data. We find that the origin of schizophrenia is complex and likely governed by different evolutionary mechanisms that are not mutually exclusive. Furthermore, the most recent evidence implies that schizophrenia cannot be comprehended as a trait that has elevated fitness in human evolutionary lineage, but has been a mildly deleterious by‐product of specific patterns of the evolution of the human brain. In other words, novel findings do not support previous hypotheses stating that schizophrenia risk genes have an evolutionary advantage. 相似文献
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Mosaicism for Dominant Collagen 6 Mutations as a Cause for Intrafamilial Phenotypic Variability 下载免费PDF全文
Sandra Donkervoort Ying Hu Tanya Stojkovic Nicol C. Voermans A. Reghan Foley Meganne E. Leach Jahannaz Dastgir Véronique Bolduc Thomas Cullup Alix de Becdelièvre Lin Yang Hai Su Katherine Meilleur Alice B. Schindler Erik‐Jan Kamsteeg Pascale Richard Russell J. Butterfield Thomas L. Winder Thomas O. Crawford Robert B. Weiss Francesco Muntoni Valérie Allamand Carsten G. Bönnemann 《Human mutation》2015,36(1):48-56
Collagen 6‐related dystrophies and myopathies (COL6‐RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter‐ and intrafamilial variable expressivity are commonly observed. We present clinical, immunohistochemical, and genetic data on four COL6‐RD families with marked intergenerational phenotypic heterogeneity. This variable expression seemingly masquerades as anticipation is due to parental mosaicism for a dominant mutation, with subsequent full inheritance and penetrance of the mutation in the heterozygous offspring. We also present an additional fifth simplex patient identified as a mosaic carrier. Parental mosaicism was confirmed in the four families through quantitative analysis of the ratio of mutant versus wild‐type allele (COL6A1, COL6A2, and COL6A3) in genomic DNA from various tissues, including blood, dermal fibroblasts, and saliva. Consistent with somatic mosaicism, parental samples had lower ratios of mutant versus wild‐type allele compared with the fully heterozygote offspring. However, there was notable variability of the mutant allele levels between tissues tested, ranging from 16% (saliva) to 43% (fibroblasts) in one mosaic father. This is the first report demonstrating mosaicism as a cause of intrafamilial/intergenerational variability of COL6‐RD, and suggests that sporadic and parental mosaicism may be more common than previously suspected. 相似文献