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81.
An Evaluation of Genetic Heterogeneity in 145 Breast-Ovarian Cancer Families 总被引:27,自引:11,他引:16
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Steven A. Narod Deborah Ford Peter Devilee Rosa B. Barkardottir Henry T. Lynch Simon A. Smith Bruce A. J. Ponder Barbara L. Weber Judy E. Garber Jill M. Birch Renee S. Cornelis David P. Kelsell Nigel K. Spurr Elizabeth Smyth Neva Haites Hagay Sobol Yves-Jean Bignon Jenny Chang-Claude Ute Hamann Annika Lindblom Ake Borg M. Steven Piver Holly H. Gallion Jeffrey P. Struewing Alice Whittemore Patricia Tonin David E. Goldgar Douglas F. Easton 《American journal of human genetics》1995,56(1):254-264
The breast-ovary cancer–family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17ql2-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%–100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer–family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations. 相似文献
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84.
Human alveolar macrophage fibronectin: synthesis, secretion, and ultrastructural localization during gelatin-coated latex particle binding 总被引:14,自引:4,他引:10
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Human pulmonary alveolar macrophages synthesized and secreted several characteristic high molecular weight proteins for at least 7 d in vitro. Immunoprecipitates of medium and cell lysates from metabolically labeled cultures with specific anti-human plasma fibronectin IgG contained one major labeled polypeptide of molecular weight 440,000 (unreduced) or 220,000 (reduced). An identical polypeptide in conditioned medium from radiolabeled macrophages bound specifically to gelatin-Sepharose, demonstrating that alveolar macrophages synthesized and secreted a molecule immunologically and functionally similar to fibronectin. Fibronectin was the major newly synthesized and secreted polypeptide of freshly harvested alveolar macrophages. Pulse-chase experiments revealed that newly synthesized fibronectin was rapidly secreted into medium, approximately 50 percent appearing by 1 h and 80 percent by 8 h. Immunoperoxidase staining using antifibronectin F(ab’)(2)-peroxidase conjugates revealed the majority of immunoreactive fibronectin to be intracellular, localized to endoplasmic reticulum and Golgi apparatus. No extracellular matrix fibronectin was visualized, and cell surface staining was rarely seen, usually appearing only at sites where cells were closely apposed and not at sites of macrophage-substrate attachment. Similar immunostaining of fibroblast cultures revealed cell surface-associated fibrillar fibronectin. Ultrastructural localization of fibronectin during binding and phagocytosis of gelatin-coated and plain latex particles revealed fibronectin only on gelatin-latex beads and at their cell binding sites. Neigher plain latex beads nor their cell membrane binding sites stained for fibronectin. These results demonstrate that fibronectin is a major product of human alveolar macrophages, is rapidly secreted, and is localized at cell membrane binding sites for gelatin-coated particles. In view of the known binding properties of fibronectin, it may serve as an endogenous opsonic factor promoting the binding of staphylococcus, denatured collagen, fibrin, or other macromolecules to macrophages in the lower respiratory tract. 相似文献
85.
On the phospholipids of Bacillus megaterium 总被引:12,自引:0,他引:12
86.
87.
Fractions of synaptosomes were used to study the regulation of -aminobutyric acid (GABA) synthesis. The isolated synaptosomes were superfused in media of various compositions. [3H]GABA and GABA released into the medium or remaining in the synaptosomes were analyzed by liquid scintillation and HPLC techniques. Different conditions, designed to increase the GABA efflux rate were used: the rate of superfusion was varied and the concentrations of K+ and Ca2+ were altered. Stimulation of GABA efflux was paralleled with an increased synthesis of GABA, since, in spite of the increased GABA efflux, a relatively constant intraterminal level was found. The findings suggest that the intraterminal concentration of GABA and thus also its synthesis is regulated via product inhibition. In addition, [3H]GABA, exogenous, and GABA, endogenous, responded to external stimulae (Ca2+, veretradine, various GABA concentrations and the glutaminase inhibitor diazo-nor-leucine) in a way which was compatible with them being localized in and/or released from different compartments. 相似文献
88.
Phylogenetic screening of the human genome: identification of differentially hybridizing repetitive sequence families 总被引:1,自引:0,他引:1
The phi-screen, a method of phylogenetic screening, can be employed to
detect repetitive sequence families that differentially hybridize between
closely related species. Such differences may involve sequence divergence
or variations in copy number, including total presence versus absence of a
family of repeated DNA. We present the results of a phi-screen comparing
the human genome to that of the prosimian, Galago crassicaudatus. Three
human repetitive families that are divergent or not present in galago have
been detected. One of these families is described in detail; it is similar
among the anthropoids but is present in a lower copy number and/or
divergent form in prosimians. The family is clearly related to the
transposon-like human element (THE) described by Paulson et al. (1985).
THEs have long terminal repeats reminiscent of retroviruses but are unique
in that they have no sequence similarity to known mammalian retroviruses.
The sequence of a solo long terminal repeat, found unassociated with THE
internal sequence, is presented. This family member, THE p2, is bordered by
a 5-bp target-site repeat and is interrupted by the insertion of an Alu
element. A solo THE element sequenced by Wiginton et al. (1986) contains an
insertion of Alu at precisely the same position as does THE p2.
相似文献
89.
The alcohol dehydrogenase (Adh) region from five planitibia subgroup
species of Hawaiian picture-wing Drosophila has been cloned. A total of 15
kb of DNA in and around the Adh gene has been compared among the five
species. Genetic distances were calculated to determine evolutionary
relationships. These distances agree with previous distances determined by
protein polymorphism and DNA hybridization techniques and can be
interpreted in terms of specific island colonization and speciation
(founder) events over the past 5 Myr. Examination of the restriction maps
of the cloned Adh region from the five species shows many instances of
small deletions, insertion of a transposable element in D. heteroneura, and
the existence of a highly variable region on the 3' side of the Adh gene.
Clustering relationships and rates of DNA change are calculated and
compared with the relationship found for other species of Drosophila.
相似文献
90.
Determination of short-chain fatty acids in serum by hollow fiber supported liquid membrane extraction coupled with gas chromatography 总被引:1,自引:0,他引:1
Zhao G Liu JF Nyman M Jönsson JA 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,846(1-2):202-208
A method based on hollow fiber supported liquid membrane extraction coupled with a gas chromatograph equipped with flame ionization detector (GC-FID) was developed for the determination of six short-chain fatty acids including acetic acid, propionic acid, i-butyric acid, n-butyric acid, i-valeric acid and n-valeric acid in serum. Hollow fiber supported liquid membrane extraction was employed for preconcentration and clean-up of the samples. The fatty acids were extracted from the acidic donor (diluted serum) into a liquid membrane formed in the wall of the hollow fiber with 10% tri-n-octylphoshphine oxide (TOPO) in di-n-hexyl ether, and then extracted back into a basic acceptor solution filled in the lumen of the hollow fiber. After being acidified with HCl, the acceptor was directly analyzed by GC-FID. The acceptor concentration, donor pH, membrane liquid and extracting time were optimized giving an enrichment factor up to 155 times. The good linearity (r(2)>0.980), reasonable recovery (87.2-121%), and satisfactory intra-assay (8.2-11.5%) and inter-assay (6.1-11.6%) precision illustrated the good performance of the present method. Limits of detection (LOD) ranged from 0.04 to 0.24 microM and limits of quantification (LOQ) varied from 0.13 to 0.80 microM. 相似文献