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991.
McManamny P Chy HS Finkelstein DI Craythorn RG Crack PJ Kola I Cheema SS Horne MK Wreford NG O'Bryan MK De Kretser DM Morrison JR 《Human molecular genetics》2002,11(18):2103-2111
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene. This disorder is characterized by degeneration of motor and sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as gynecomastia and reduced fertility. We describe the development of a transgenic model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR(65)) or 120 CAG repeats (AR(120)), with widespread expression driven by the cytomegalovirus promoter. Mice carrying the AR(120) transgene displayed behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a mild phenotype. Progressive muscle weakness and atrophy was observed in AR(120) mice and was associated with the loss of alpha-motor neurons in the spinal cord. There was no evidence of neurodegeneration in other brain structures. Motor dysfunction was observed in both male and female animals, showing that in SBMA the polyglutamine repeat expansion causes a dominant gain-of-function mutation in the AR. The male mice displayed a progressive reduction in sperm production consistent with testis defects reported in human patients. These mice represent the first model to reproduce the key features of SBMA, making them a useful resource for characterizing disease progression, and for testing therapeutic strategies for both polyglutamine and motor neuron diseases. 相似文献
992.
993.
Comparative genomic hybridization pattern distinguishes T-cell/histiocyte-rich B-cell lymphoma from nodular lymphocyte predominance Hodgkin's lymphoma 总被引:3,自引:0,他引:3 下载免费PDF全文
Franke S Wlodarska I Maes B Vandenberghe P Achten R Hagemeijer A De Wolf-Peeters C 《The American journal of pathology》2002,161(5):1861-1867
Several lines of evidences suggest that T cell/histiocyte-rich B-cell lymphoma (T/HRBCL) represents an aggressive variant of the clinically indolent entity nodular lymphocyte predominance Hodgkin's lymphoma (LPHL). Still, this view has not yet been supported by firm genetic evidence. In this study, we analyzed 17 T/HRBCL cases using comparative genomic hybridization (CGH) combined with microdissection of single CD20+ neoplastic cells and DNA amplification by degenerate oligonucleotide primed-polymerase chain reaction, an approach we previously used in LPHL. Genomic imbalances were detected in all cases (in total, 80 changes). The most common imbalances included gain of Xq, 4q13q28, Xp21p11, and 18q21, and loss of 17p. Of note, a partial gain of 4q, a rare change in lymphoma, is also among the genomic imbalances most frequently encountered in LPHL. On the other hand, the CGH profiles of T/HRBCL and LPHL showed several distinct features, in particular with respect to the number of genomic imbalances (average of 4.7 in T/HRBCL versus 10.8 in LPHL) and their distribution (usually 1 to 5 in T/HRBCL versus 6 to 22 in LPHL). Altogether, our CGH findings of shared as well as distinctive cytogenetic features in both diseases suggest that T/HRBCL constitutes a separate lymphoma entity, possibly originating from the same precursor cell as LPHL. 相似文献
994.
Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome 下载免费PDF全文
Early-onset cataract and Alzheimer's disease occur with high frequency in Down syndrome (trisomy 21), the most common chromosome duplication in human live births. Previously, we used in vivo and lens organ culture models to demonstrate Alzheimer pathophysiology in oxidative stress-related lens degeneration. Currently, well-characterized Alzheimer transgenic mouse models are used to extend these findings. Here, we report on mice carrying a complete copy of a wild-type human AbetaPP (hAbetaPP) gene from the Down syndrome critical region on chromosome 21. hAbetaPP mice produce fiber cell membrane defects similar to those described in human cataracts and increased age-related lens degeneration. hAbetaPP expression and mRNA alternative splicing in human and mouse lens and cornea favor longer, potentially more amyloidogenic forms. Endogenous mouse AbetaPP expression is increased in transgenic lenses, consistent with the cycle of oxidative stress proposed in the mechanism of Alzheimer pathophysiology. Alternative splicing previously designated as neuron-specific occurs in human lens and cornea, and is maintained by hAbetaPP expressed in mouse tissues. These present data implicate AbetaPP in fiber cell formation and in early-onset cataracts in Down syndrome. Finally, our findings provide further support for our hypothesis that Alzheimer pathophysiology contributes to the cataract formation that is increasing in the aging population. 相似文献
995.
Summary Extracts of S. cerevisiae cells can catalyze homologous recombination between plasmids in vitro. Extracts prepared from rad50, rad52 or rad54 disruption mutants all have reduced recombinational activity compared to wild-type. The rad52 and rad54 extracts are more impaired in the recombination of plasmids containing double-strand breaks than of intact plasmids, whereas rad50 extracts are deficient equally for both types of substrate. The nuclease RhoNuc (previously designated yNucR), encoded by the RNC1 (previously designated NUC2) gene and regulated by the RAD52 gene, is not required for recombination when one substrate is single-stranded but is essential for the majority of recombination events when both substrates are double-stranded. Furthermore, elimination of this nuclease restores recombination in rad52 extracts to levels comparable to those in wild-type extracts. 相似文献
996.
The establishment of a health surveillance system for the single homeless is described. Health checks were performed in two Salvation Army hostels by a district nurse supported by general practitioners and other workers from one health centre. High levels of morbidity were discovered and the residents were largely treated by the primary health care team. Those residents who were referred to other agencies were shown to have a high attendance rate. An open access clinic was later set up by the district nurse in one of the hostels. This was well received by residents and staff and reduced the call out rate for the general practitioners.
In some parts of the UK, special medical centres for the single homeless have been established on the premiss that it is unrealistic to expect general practitioners to provide an adequate service. However, this study describes an effective service based on primary care which is acceptable to homeless people while being relatively cheap and easy to administer. We recommend the development of a peripatetic service as outlined in this study, offering health care at hostels, day centres and other places where the homeless are to be found.
相似文献997.
Potential of a Simplified p24 Assay for Early Diagnosis of Infant Human Immunodeficiency Virus Type 1 Infection in Haiti 下载免费PDF全文
998.
999.
A 2-year-old male child with mosaicism for monosomy of chromosome 22 is described. He had moderate psychomotor retardation, generalised hypotonia, large ears, epicanthus, synophrys, and cutaneous syndactyly between all the fingers. 相似文献
1000.
Christian Stock Birgit Gassner Christof R. Hauck Hannelore Arnold Sabine Mally Johannes A. Eble Peter Dieterich Albrecht Schwab 《The Journal of physiology》2005,567(1):225-238
Their glycolytic metabolism imposes an increased acid load upon tumour cells. The surplus protons are extruded by the Na+ /H+ exchanger (NHE) which causes an extracellular acidification. It is not yet known by what mechanism extracellular pH (pHe ) and NHE activity affect tumour cell migration and thus metastasis. We studied the impact of pHe and NHE activity on the motility of human melanoma (MV3) cells. Cells were seeded on/in collagen I matrices. Migration was monitored employing time lapse video microscopy and then quantified as the movement of the cell centre. Intracellular pH (pHi ) was measured fluorometrically. Cell–matrix interactions were tested in cell adhesion assays and by the displacement of microbeads inside a collagen matrix. Migration depended on the integrin α2β1. Cells reached their maximum motility at pHe ∼7.0. They hardly migrated at pHe 6.6 or 7.5, when NHE was inhibited, or when NHE activity was stimulated by loading cells with propionic acid. These procedures also caused characteristic changes in cell morphology and pHi . The changes in pHi , however, did not account for the changes in morphology and migratory behaviour. Migration and morphology more likely correlate with the strength of cell–matrix interactions. Adhesion was the strongest at pHe 6.6. It weakened at basic pHe , upon NHE inhibition, or upon blockage of the integrin α2β1. We propose that pHe and NHE activity affect migration of human melanoma cells by modulating cell–matrix interactions. Migration is hindered when the interaction is too strong (acidic pHe ) or too weak (alkaline pHe or NHE inhibition). 相似文献