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排序方式: 共有930条查询结果,搜索用时 15 毫秒
21.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
22.
Human mini-chromosomes in mouse embryonal stem cells 总被引:3,自引:2,他引:3
We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb
in size into mouse embryonal stem cells. Although these human mini-
chromosomes are stable in hamster and chicken cells, they re-arrange or
segregate aberrantly in the embryonal stem cells and are rapidly lost in
the absence of selection. However, one of the mini-chromosomes re-
arranged, acquired mouse centromeric sequences and was then stably
maintained for at least 60 population doublings in culture. This mini-
chromosome, which is 4 Mb in size, is a candidate for a mouse germ line
chromosome vector.
相似文献
23.
Louise R Rodino-Klapac Paul ML Janssen Chrystal L Montgomery Brian D Coley Louis G Chicoine K Reed Clark Jerry R Mendell 《Journal of translational medicine》2007,5(1):45-11
Background
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. 相似文献24.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
25.
Peptide specificity and HLA restriction do not dictate lymphokine production by allergen-specific T-lymphocyte clones. 总被引:1,自引:0,他引:1
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R J van Neerven M M van de Pol E A Wierenga R C Aalberse H M Jansen M L Kapsenberg 《Immunology》1994,82(3):351-356
Human and murine CD4+ T lymphocytes can be subdivided into distinct subsets [T-helper type 0 (Th0), Th1 or Th2], based on their lymphokine production profiles. Not much is known about the factors that determine these restricted lymphokine secretion profiles. Peptide specificity and human leucocyte antigen (HLA) restriction may be such factors. As it is well established that allergen-specific T lymphocytes from atopic individuals and non-atopic controls differ in their lymphokine secretion profile, we studied two allergen-specific T-lymphocyte clones (TLC) with identical peptide specificity and HLA restriction that were generated from the peripheral blood of an atopic donor and a non-atopic control donor. The two CD4+ TLC recognize the same epitope (20-33) of the house dust mite Dermatophagoides pteronyssinus major allergen Der p II. Both TLC recognize the epitope in an HLA-DQB1*0602-restricted manner. However, the lymphokine production profiles of these TLC show clear differences after allergen-specific or polyclonal activation. As expected, TLC JBD4 from the atopic donor produced high levels of interleukin-4 (IL-4) without detectable interferon-gamma (IFN-gamma), whereas TLC PBA1 from the non-atopic donor produced both IFN-gamma and IL-4 upon allergen-specific or polyclonal activation. Inasmuch as both TLC recognized the same epitope of Der p II in association with the same HLA-DQ molecule, these data suggest that peptide specificity and HLA restriction of human allergen-specific TLC do not dictate their lymphokine secretion profile. 相似文献
26.
Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings. 相似文献
27.
Dendritic cell-mediated T cell polarization 总被引:24,自引:0,他引:24
Effective defense against diverse types of micro-organisms that invade our body requires specialized classes of antigen-specific immune responses initiated and maintained by distinct subsets of effector CD4+ T helper (Th) cells. Excessive or detrimental (e.g., autoimmune) responses by effector T cells are controlled by regulatory T cells. The optimal balance in the development of the different types of effector and regulatory Th cells is orchestrated by dendritic cells (DC). This review discusses the way DC adapt the T cell response to the type of pathogen, focusing on the tools that DC use in this management of the T cell response. 相似文献
28.
Needle biopsy of renal allografts: comparison of two techniques 总被引:2,自引:0,他引:2
Bogan ML; Kopecky KK; Kraft JL; Holladay AO; Filo RS; Leapman SB; Thomalla JV 《Radiology》1990,174(1):273-275
Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications. 相似文献
29.
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