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51.
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52.
Riley NE Bardag-Gorce F Montgomery RO Li J Lungo W Lue YH French SW 《Experimental and molecular pathology》2003,74(2):173-179
Mallory bodies are cytokeratin-ubiquitin aggresomes that form in hepatocytes in many different chronic liver diseases. One of the key components in aggresome formation, not yet investigated in Mallory body formation, is the role of microtubules. An in vitro tissue culture assay is required to test for microtubule involvement in Mallory body formation so that Mallory body formation can be observed in the presence or absence of microtubule-disrupting agents. In this report, a new model of in vitro Mallory body formation was developed, which uses cultured hepatocytes isolated from drug-primed mice. When hepatocytes were incubated in the presence of antimicrotubule agents, they failed to form Mallory bodies. It is concluded that intact microtubules are required for Mallory body formation. 相似文献
53.
Is there a way for pathologists to decrease interobserver variability in the diagnosis of dysplasia?
Montgomery E 《Archives of pathology & laboratory medicine》2005,129(2):174-176
Many obstacles interfere with our efforts to screen patients with Barrett esophagus. Probably the largest is choosing the appropriate patient group for screening. Beyond this problem, sampling error on the part of endoscopists is probably more serious a problem than observer variation among pathologists reviewing patient samples. Pathologists agree well on lesions that merit close follow-up or other intervention (high-grade dysplasia and invasive carcinoma), although interobserver agreement between pathologists interpreting lesser lesions is not good. This lack of agreement is not likely to improve substantially, and many adjunct markers are being sought in an attempt to identify patients with lesions of lower grades that are most likely to progress, allowing doctors to identify patients who would benefit from upgraded surveillance. 相似文献
54.
L1 is a neural cell adhesion molecule (CAM) known to be important for normal neurological development. Despite being described as a neural CAM, we have documented L1 expression by antigen-presenting cells of myelomonocytic origin. Here we demonstrate that L1 can function as a costimulatory molecule in T cell activation. A monoclonal antibody that abrogates L1-L1 homophilic binding significantly reduced mixed leukocyte responses initiated by allogeneic L1+ dendritic cells. Autologous T cell activation in response to phytohemagglutinin was also inhibited by blockade of L1. In accordance with these results, transfection of human L1 into a murine myeloma cell line significantly increased the capacity of these cells to stimulate xenogeneic T cell responses. As a costimulatory ligand L1 could represent a novel target for immunotherapeutic intervention and may act as an important intermediary in neuroimmunological processes and disease. 相似文献
55.
A novel method for making "tissue" microarrays from small numbers of suspension cells. 总被引:1,自引:0,他引:1
Kelli Montgomery Shuchun Zhao Matt van de Rijn Yasodha Natkunam 《Applied immunohistochemistry & molecular morphology》2005,13(1):80-84
Tissue microarrays (TMAs) are a highly efficient method for large-scale protein expression studies. To date most TMAs have been constructed using paraffin-embedded specimens. The authors developed a method that allows construction of TMAs from small numbers of cells in suspension. Spun pellets of 1x10 to 1x10 cells are directly processed and embedded in paraffin in an Eppendorf tube. Cylindrical cores of 0.6 mm are taken from these tubes and embedded in a recipient paraffin block to create a TMA. This relatively simple but versatile method enables very small numbers of cells in suspension to be analyzed using the TMA technology and allows for the study of hematolymphoid and related disorders of the blood and bone marrow for which solid tissue samples cannot be readily obtained. With the increasing trend toward obtaining small samples for screening and diagnostic purposes, this method provides a means to manipulate small volume samples for high-throughput immunohistochemical analysis. This method is also amenable for use for cultured cells. 相似文献
56.
Andrea A. Zachary Robert A. Montgomery Mary S. Leffell 《Clinical and Applied Immunology Reviews》2005,5(6):373
Sensitization to antigens of the HLA and ABO system has been the biggest barrier to access in renal transplantation and, increasingly, in transplantation of other organs. Additionally, antibody to donor antigens has been shown to result in injury to the graft ranging from catastrophic, irreversible hyperacute rejection to the slower, more insidious, chronic form of rejection. The problem of access has been recognized globally and has been the incentive for measures to overcome the disadvantage experienced by the sensitized patient. However, early attempts to reduce sensitization achieved only transient success. Newer immunosuppressive agents that affect B-cell function or viability have permitted the development of treatment protocols to eliminate and, potentially, downregulate donor-specific antibodies. The use of these protocols has achieved successful transplants that were HLA and/or ABO incompatible prior to treatment and, as such, has provided some patients with their only opportunity for transplantation. 相似文献
57.
Pathogenesis of Shigella diarrhea: rabbit intestinal cell microvillus membrane binding site for Shigella toxin 总被引:4,自引:2,他引:4
G Fuchs M Mobassaleh A Donohue-Rolfe R K Montgomery R J Grand G T Keusch 《Infection and immunity》1986,53(2):372-377
This study examined the binding of purified 125I-labeled shigella toxin to rabbit jejunal microvillus membranes (MVMs). Toxin binding was concentration dependent, saturable, reversible, and specifically inhibited by unlabeled toxin. The calculated number of toxin molecules bound at 4 degrees C was 7.9 X 10(10) (3 X 10(10) to 2 X 10(11))/micrograms of MVM protein or 1.2 X 10(6) per enterocyte. Scatchard analysis showed the binding site to be of a single class with an equilibrium association constant, K, of 4.7 X 10(9) M-1 at 4 degrees C. Binding was inversely related to the temperature of incubation. A total of 80% of the labeled toxin binding at 4 degrees C dissociated from MVM when the temperature was raised to 37 degrees C, but reassociated when the temperature was again brought to 4 degrees C. There was no structural or functional change of MVM due to toxin as monitored by electron microscopy or assay of MVM sucrase activity. These studies demonstrate a specific binding site for shigella toxin on rabbit MVMs. The physiological relevance of this receptor remains to be determined. 相似文献
58.
59.
Montgomery GW Zhao ZZ Morley KI Marsh AJ Boomsma DI Martin NG Duffy DL 《Human reproduction (Oxford, England)》2003,18(11):2460-2464
BACKGROUND: Folate metabolism is critical to embryonic development, influencing neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with dizygotic (DZ) twinning through pregnancy loss. METHODS: The C677T and A1298C polymorphisms in MTHFR were genotyped in 258 Australasian families (1016 individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and a population sample of 462 adolescent twin families (1861 individuals). Haplotypes were constructed from the alleles, and transmission of the MTHFR haplotypes to mothers of DZ twins and from parents to twins in the adolescent twin families analysed. RESULTS: The C677T and A1298C were common in all three populations (frequencies > 0.29). There was strong linkage disequilibrium (D' = 1) between the variants, showing that specific combinations of alleles (haplotypes) were transmitted together. Three haplotypes accounted for nearly all the variation. There was no evidence of any association between MTHFR genotype and twinning in mothers of twins, or of the loss of specific MTHFR genotypes during twin pregnancies. CONCLUSIONS: It is concluded that variation in twinning frequency is not associated with MTHFR genotype. 相似文献
60.
The clients, aides, and staff of a homemaker services program for the rural frail elderly were individually interviewed concerning client's met and unmet needs. While the overall response from all three groups suggested a highly effective program, significant differences existed among the three groups with regard to what they considered the most important needs, both met and unmet by the program. It was concluded that although the perceptions of all three groups of participants in such programs might differ, such differences may not necessarily work to undermine the program. 相似文献