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71.
Reorganization of human cortical maps caused by inherited photoreceptor abnormalities 总被引:3,自引:0,他引:3
We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization. 相似文献
72.
Lee MH Gordon D Ott J Lu K Ose L Miettinen T Gylling H Stalenhoef AF Pandya A Hidaka H Brewer B Kojima H Sakuma N Pegoraro R Salen G Patel SB 《European journal of human genetics : EJHG》2001,9(5):375-384
Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM. 相似文献
73.
William Walker Craig W. Roberts James M. Brewer James Alexander 《European journal of immunology》1995,25(5):1426-1430
These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient (PBL-SCID) mice following vaccination with antigen from the protozoan parasite Toxoplasma gondii. To determine the effect of previous exposure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a single T. gondii-seronegative or a single seropositive donor. These reconstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicles as an immunological adjuvant. Animals were bled at pre-determined time points post-vaccination and the expression of human anti-STAg antibodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both groups of reconstituted animals, although the pattern of isotype production differed markedly between groups. The response in animals reconstituted with lymphocytes from the T. gondii-seronegative donor consisted primarily of IgM and subsequently of IgG (predominantly IgG1). In animals reconstituted with lymphocytes from the seropositive donor, no parasite-specific IgM could be demonstrated. The detectable response to STAg consisted entirely of human antibodies of the IgG isotype (IgG1), indicative of a memory-type response. These results mimicked exactly the antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectious agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and secondary responses of the human donors. 相似文献
74.
Fluorescence in situ hybridization investigation of cutaneous lesions in acute promyelocytic leukemia. 总被引:1,自引:0,他引:1
Joanna E Wrede Uma Sundram Sabine Kohler Athena M Cherry Daniel A Arber Tracy I George 《Modern pathology》2005,18(12):1569-1576
Cutaneous manifestations of acute promyelocytic leukemia are rare but well documented. Skin biopsies of leukemia can be difficult to confirm using morphology alone, and paraffin section immunophenotyping is not specific in separating acute promyelocytic leukemia from other acute myeloid leukemias involving the skin or inflammatory conditions, such as Sweet's syndrome and all-trans retinoic acid-associated genital ulcers, which may mimic leukemia cutis. Fluorescence in situ hybridization has been shown to be a fast and effective method of detecting the PML/RARA fusion gene characteristic of acute promyelocytic leukemia in fresh blood and bone marrow samples. Fluorescence in situ hybridization has also been demonstrated to be effective in detecting other chromosomal rearrangements in paraffin-embedded tissue. This retrospective study of cutaneous lesions from four patients with acute promyelocytic leukemia evaluates the utility of performing fluorescence in situ hybridization to confirm the presence of cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed, paraffin-embedded skin biopsies. All patients had previous bone marrow findings of acute promyelocytic leukemia with characteristic morphology, immunophenotype, and cytogenetic studies, which detailed the presence of the t(15;17)(q22;q12) rearrangement. Two skin biopsies showed an infiltrate of blastic cells involving the dermis in a diffuse pattern and one biopsy had a perivascular/periadnexal pattern. The fourth case, involving the scrotum, showed a predominant neutrophilic infiltrate diffusely involving the dermis and epidermis with a subset of blastic cells. Nuclei were extracted from core biopsies of the formalin-fixed paraffin-embedded tissue and fluorescence in situ hybridization was performed using a dual color, dual fusion PML / RARA probe. All cases showed evidence of the t(15;17) rearrangement, with 90, 79, 51 and 16% positive signal patterns, each well above background limits. Fluorescence in situ hybridization appears to be a robust technique to detect cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed paraffin-embedded skin biopsies. 相似文献
75.
Emerging electronic health record models present numerous challenges to health care systems, physicians, and regulators. This article provides explanation of some of the reasons driving the development of the electronic health record, describes two national electronic health record models (currently developing in the United States and Australia) and one distributed, personal model. The US and Australian models are contrasted in their different architectures ("pull" versus "push") and their different approaches to patient autonomy, privacy, and confidentiality. The article also discusses some of the professional, practical, and legal challenges that health care providers potentially face both during and after electronic health record implementation. 相似文献
76.
Zabka TS Romano TA 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2003,273(1):636-647
The skin is an important tissue of the immune system; however, little is known about immune cells in dolphin skin, and very few cetacean-specific immunoreagents are available for investigative purposes. Therefore, in this study immunohistochemistry techniques were used with species-specific and non-species-specific antibodies to characterize immune cells, primarily focusing on Langerhans cells, in skin from the Atlantic bottlenose dolphin (Tursiops truncatus). An antibody to human major histocompatibility complex (MHC) class II molecules labeled cells with a dendritic-like morphology. The immunophenotype, morphology, and distribution of some of these cells are consistent with those of Langerhans cells. The cells were predominantly found in dermal papillae, primarily along the epidermal-dermal junction. Thus, the location of these cells was somewhat different from that in terrestrial mammals. Other MHC II (+) cells of varying morphology were observed deeper in the dermis, with a perivascular concentration, and had characteristics of macrophages and dermal dendritic cells. There was no immunostaining with cetacean-specific CD2 or CD21. In diseased skin, a subjective increase of MHC II (+) cells, most notably in the superficial skin layers, was associated with an ulcerative dermatitis. A few CD2 (+) cells were also present. Differences between dolphins and terrestrial mammals in terms of morphology, mechanisms of response to insult and repair, and environmental challenges may explain the modified distribution of MHC II (+) cells in dolphin skin. An elucidation of the immune cells in cetacean skin will contribute to our understanding of the evolution of functional adaptations to various environments, facilitate diagnosis of skin diseases, and define the potential for intradermal administration of vaccines and other immunotherapeutics. 相似文献
77.
In Vivo Complementation of ureB Restores the Ability of Helicobacter pylori To Colonize 总被引:4,自引:0,他引:4
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Kathryn A. Eaton Joanne V. Gilbert Elizabeth A. Joyce Amy E. Wanken Tracy Thevenot Patrick Baker Andrew Plaut Andrew Wright 《Infection and immunity》2002,70(2):771-778
The objective of this study was to determine (i) if complementation of ureB-negative Helicobacter pylori restores colonization and (ii) if urease is a useful reporter for promoter activity in vivo. Strains used were M6, M6DeltaureB, and 10 recombinant derivatives of M6 or M6DeltaureB in which urease expression was under the control of different H. pylori promoters. Mice were orally inoculated with either the wild type or one of the mutant strains, and colonization, in vivo urease activity, and extent of gastritis were determined. Of eight M6DeltaureB recombinants tested, four colonized mice. Of those, three had the highest in vitro urease activity of any of the recombinants, significantly different from that of the noncolonizing mutants. The fourth colonizing recombinant, with ureB under control of the cag-15 promoter, had in vitro urease activity which did not differ significantly from the noncolonizing strains. In vivo, urease activities of the four colonizing transformants and the wild-type control were indistinguishable. There were no differences in gastritis or epithelial lesions between mice infected with M6 and those infected with the transformants. These results demonstrate that recovery of urease activity can restore colonizing ability to urease-negative H. pylori. They also suggest that cag-15 is upregulated in vivo, as was previously suggested by demonstrating that it is upregulated upon contact with epithelial cells. Finally, our results suggest that total urease activity and colonization density do not contribute to gastritis due to H. pylori. 相似文献
78.
Janet Audrain Caryn Lerman Andres Gomez-Caminero Neal R. Boyd C. Tracy Orleans 《Journal of Applied Biobehavioral Research》1998,3(1):29-42
Studies point to an association between anxiety and smoking. However, the mechanisms linking trait anxiety and nicotine dependence have not been evaluated fully. Potential mediators include self-medication variables (e.g., use of nicotine to manage anxiety) and cognitive variables (e.g., lower levels of self-efficacy). The present study explored these mechanisms in a sample of 352 male and female smokers. The results showed that trait anxiety correlated significantly with negative affect smoking (r= .29, p= .0001), stimulation smoking (r=.15, p = .007), and nicotine dependence (r= .20, p= .0003). Trait anxiety also correlated significantly with self-efficacy (r =-.22, p = .0003). Regression analyses revealed that trait anxiety predicted nicotine dependence after controlling for depression, education, race, age, and marital status (R2= .09, p = .0001). Path modeling indicated that both negative affect smoking and quitting self-efficacy mediated the relationship between trait anxiety and nicotine dependence. Interventions that emphasize the management of anxious mood and quitting confidence may benefit anxious smokers. 相似文献
79.
Laurie Miller Brotman Kathleen Kiely Gouley Daniel Chesir-Teran Tracy Dennis Rachel G Klein Patrick Shrout 《Journal of clinical child and adolescent psychology》2005,34(4):724-734
This study investigated the immediate impact of an 8-month center- and home-based prevention program for preschoolers at high risk for conduct problems. We report immediate program effects on observed and self-rated parenting practices and observed child behavior with peers. Ninety-nine preschool-age siblings of adjudicated youths and their families were randomly assigned to an enhanced version of the Incredible Years Series (Webster-Stratton, 1989; n = 50) or to a no-intervention control condition (n = 49). In an intent-to-treat design, the intervention yielded significant effects on negative parenting, parental stimulation for learning, and child social competence with peers. Improvements in negative parenting, stimulation for learning, and child social competence support the potential of the intervention to prevent later conduct problems in high-risk children. 相似文献
80.
E J Brewer E H Giannini N Kuzmina L Alekseev 《The New England journal of medicine》1986,314(20):1269-1276
One hundred sixty-two children with severe juvenile rheumatoid arthritis were entered in a randomized, double-blind, placebo-controlled 12-month clinical trial designed to establish the efficacy and safety of two slower-acting antirheumatic drugs, penicillamine and hydroxychloroquine. The study was a cooperative effort of the United States and the Soviet Union. One group of subjects received 10 mg of penicillamine per kilogram of body weight per day, another group received 6 mg of hydroxychloroquine per kilogram daily, and a third group received placebo. All three groups were allowed a single concurrent nonsteroidal antiinflammatory drug, but no other antirheumatic medications, including corticosteroids. All three groups had dramatic improvement in many of the clinical and laboratory outcome variables after one year of study. There were no significant differences in efficacy between the penicillamine and placebo groups. Pain on movement was the only index of articular disease that was alleviated more by hydroxychloroquine than by placebo. Serious adverse drug reactions attributable to the active agents were rare. We were unable to demonstrate that, in the presence of a nonsteroidal antiinflammatory drug, either penicillamine or hydroxychloroquine is superior to placebo in the treatment of children with juvenile rheumatoid arthritis. 相似文献