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161.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献
162.
N E Morton D Chiu C Holland P A Jacobs D Pettay 《American journal of medical genetics》1987,28(2):353-360
Reproductive histories and chromosomes of spontaneous abortions were studied by segregation analysis in 1890 sibships ascertained through a cytogenetically studied abortion. Normal karyotypes are associated with recurrent abortion. Among abnormal karyotypes, trisomy has an elevated recurrence risk even after adjustment through a liability indicator for maternal age. Possible mechanisms and conflicting evidence in the literature on trisomy are discussed. None of these differences in recurrence risk is large enough to play a significant numerical role in genetic counseling. 相似文献
163.
D Hassine G Rougereau JM Feron MC Henry-Feugeas V Fabre JC Sadik E Schouman-Claeys 《Surgical and radiologic anatomy : SRA》1994,16(3):293-301
Summary The angular points are the ligamentous and tendinous structures that reinforce the posteromedial and posterolateral capsule of the knee and share in fixation of the posterior horns of the menisci. They are often damaged in acute injuries and this is usually associated with ruptures of the cruciate and collateral ligaments and may add to the degree of laxity. We describe the normal appearance of these structures in terms of the sectional anatomy, correlated with the lesional appearances of complete and incomplete ruptures and associated meniscal detachments as shown by clinical testing and arthrotomy findings.
IRM des points d'angle du genou : bases anatomiques et applications aux genoux traumatiques
Résumé Les points d'angle sont des structures ligamentaires et tendineuses qui renforcent la capsule postéro-médiale et postéro-latérale et participent à la fixation des cornes postérieures des ménisques. Leurs lésions, fréquentes au cours des traumatismes aigus, sont généralement associées à des ruptures des ligaments croisés et des ligaments collatéraux et peuvent être source d'une aggravation de la laxité. Nous rapportons, en corrélation avec l'anatomie en coupe, l'aspect normal de ces structures, et en corrélation avec les données de l'arthrotomie et du testing les aspects lésionnels observés au cours des traumatismes : ruptures complètes, incomplètes et désinsertions méniscales associées.相似文献
164.
Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein 总被引:9,自引:0,他引:9 下载免费PDF全文
Thuring CM Erkens JH Jacobs JG Bossers A Van Keulen LJ Garssen GJ Van Zijderveld FG Ryder SJ Groschup MH Sweeney T Langeveld JP 《Journal of clinical microbiology》2004,42(3):972-980
A procedure for discrimination between scrapie and bovine spongiform encephalopathy (BSE) in sheep is of importance for establishing whether BSE has entered the sheep population. Since BSE has not yet been found in sheep at the farm level, such discrimination procedures can be developed only with experimental sheep BSE. Two distinctive molecular features of the prion protein (PrP)-molecular size and glycosylation profile-in proteinase K digests of brain stem tissue from sheep were used here; upon Western blotting, these features led to an unequivocal discrimination among natural scrapie, experimental scrapie, and experimental BSE. The higher electrophoretic mobility of PrP in sheep BSE could be best observed after deglycosylation treatment with N-glycosidase F. A simpler method for confirmation of this size difference involved comparison of the ratios for the binding of two monoclonal antibodies: P4 and 66.94b4. Based on epitope mapping studies with P4 and peptides, it appeared that N-terminal amino acid sequence WGQGGSH was intact only in sheep scrapie digests. Another feature typical for PrP in sheep BSE was the large fraction of diglycosylated PrP (70% or more). These data were obtained for a large group of positive sheep, consisting of 7 sheep with experimental BSE infection (genotypes: six ARQ/ARQ and one AHQ/AHQ), 48 sheep naturally infected with scrapie (six different genotypes), and 3 sheep with primary experimental scrapie infection. Routine tests of slaughter material serve well for the initial detection of both BSE and scrapie. With Western blotting as a rapid follow-up test, a 66.94b4/P4 antibody binding ratio above 1.5 is a practical indicator for serious suspicion of BSE infection in sheep. 相似文献
165.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
166.
167.
In cybrid cells carrying the mitochondrial A3243G MELAS mutation, which were also heteroplasmic for the G12300A suppressor mutation, we observed a transient episode of heteroplasmic instability, resulting in a wide diversification in G12300A heteroplasmy levels and a shift in the average heteroplasmy level from 11 to 29%. These cells were found to be trisomic for chromosome 9, whereas a minority of cells that retained disomy-9 showed no instability. Coculture experiments implied that trisomy-9 cells exhibited a significant growth advantage, but neither heteroplasmy levels, respiratory phenotype nor trisomy-9 itself had direct selective value under standard culture conditions. Mitochondrial nucleoid number was the same (50–100) in cells that had or had not experienced transient heteroplasmic instability, but 1–2 orders of magnitude less than the segregation number in such cells. These findings support the idea that mtDNA partition is under nuclear genetic control, and implicate a locus on chromosome 9 in this regulation. 相似文献
168.
Reliable high risk HPV DNA testing by polymerase chain reaction: an intermethod and intramethod comparison 总被引:7,自引:0,他引:7 下载免费PDF全文
Jacobs MV Snijders PJ Voorhorst FJ Dillner J Forslund O Johansson B von Knebel Doeberitz M Meijer CJ Meyer T Nindl I Pfister H Stockfleth E Strand A Wadell G Walboomers JM 《Journal of clinical pathology》1999,52(7):498-503
BACKGROUND: The development of a reproducible, sensitive, and standardised human papillomavirus (HPV) polymerase chain reaction (PCR) test is required to implement HPV testing in cervical cancer screening programmes and for triaging women with mild to moderate dysplasia. AIMS: To determine the intermethod agreement between different GP5+/6+ and MY09/11 PCR based protocols for the detection and typing of high risk (HR) HPV DNA in cervical smears and to assess the intramethod reproducibility of the GP5+/6+ PCR enzyme immunoassay (EIA) for HR-HPV detection. METHODS: For the intermethod comparison, crude aliquots of 20 well characterised cervical smears comprising five HPV negative samples, and six and nine samples containing single and multiple HPV infections, respectively, were coded and sent from reference laboratory (A) to three other laboratories. One of these (laboratory B) used the GP5+/6+ PCR-EIA and was provided with standard protocols. Another laboratory (C) used GP5+/6+ PCR combined with sequence analysis and type specific PCR, whereas two laboratories (D and E) used MY09/11 PCR followed by restriction fragment length polymorphism (RFLP) analysis for the detection and typing of HR-HPV. The intramethod agreement of GP5+/6+ PCR-EIA was analysed in a subsequent study with four other laboratories (F to I) on crude aliquots of 50 well characterised cervical smears, consisting of 32 HR-HPV positive and 18 HPV negative samples. Standardised protocols, primers, and probes were also provided by the reference laboratory for HR-HPV detection. RESULTS: In the intermethod comparison, pairwise agreement of the different laboratories with reference laboratory A for the detection of HR-HPV varied between 75% and 100% (kappa values: 0.5 to 1). Typing data revealed a broader range in pairwise agreement rates between 32% and 100%. The highest agreement was found between laboratories A and B using standardised protocols and validated reagents. In the intramethod evaluation, pairwise comparison of the laboratories F to I with reference laboratory A revealed excellent agreement rates from 92% to 100% (kappa values: 0.88 to 1.0) with an overall sensitivity of 97.5% (195/200) and specificity of 99.5% (199/200). CONCLUSIONS: The detection of HR-HPV as a group is highly reproducible with GP5+/6+ PCR-EIA provided that standardised protocols and validated reagents are used. 相似文献
169.
Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases 总被引:5,自引:2,他引:5
Huang JQ; Trasler JM; Igdoura S; Michaud J; Hanal N; Gravel RA 《Human molecular genetics》1997,6(11):1879-1885
Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative
diseases resulting from the inability to catabolize GM2 ganglioside by
beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit
(Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B
(beta beta homodimer) is also defective in Sandhoff disease. We previously
developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs)
mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff)
mice succumb to a profound neurodegenerative disease by 4-6 months of age.
Here we find that neuron death in Hexb-/- mice is associated with apoptosis
occurring throughout the CNS, while Hexa-/- mice were minimally involved at
the same age. Studies of autopsy samples of brain and spinal cord from
human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances,
in keeping with the severe expression of both diseases. We suggest that
neuron death is caused by unscheduled apoptosis, implicating accumulated
GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
相似文献
170.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献