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611.
The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q 总被引:4,自引:0,他引:4
Kibar Z; Der Kaloustian VM; Brais B; Hani V; Fraser FC; Rouleau GA 《Human molecular genetics》1996,5(4):543-547
Hidrotic ectodermal dysplasia (HED), Clouston type, is an autosomal
dominant skin disorder which is most common in the French-Canadian
population and is characterized by hair defects, nail dystrophy and
palmoplantar hyperkeratosis. Biophysical and biochemical studies conducted
in HED suggested a molecular abnormality of keratins. We tested eight
French-Canadian families segregating HED for linkage to microsatellite
markers flanking the known keratin genes and were able to exclude linkage
to these loci. Therefore, a genome-wide search for the HED gene was
initiated. The first lod score above 3.00 was obtained with the marker
D13S175 located in the pericentromeric region of chromosome 13q (Zmax =
8.12 at zero recombination). The cumulative lod scores were above 3.00 for
six other markers in the region. A multipoint linkage analysis using the
markers D13S175, D13S141 and D13S143 gave a maximum lod score of 11.12 at
D13S141 with the one-lod- unit support interval spanning a 12.7 cM region
which includes D13S175 and D13S141. Haplotype analysis allowed us to
establish D13S143 as the telomeric flanking marker for the HED candidate
region.
相似文献
612.
613.
Desirée A. Benefield Scott K. Dessain Nancy Shine Melanie D. Ohi D. Borden Lacy 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(14):5630-5635
Botulinum neurotoxin (BoNT) is produced by Clostridium botulinum and associates with nontoxic neurotoxin-associated proteins to form high-molecular weight progenitor complexes (PCs). The PCs are required for the oral toxicity of BoNT in the context of food-borne botulism and are thought to protect BoNT from destruction in the gastrointestinal tract and aid in absorption from the gut lumen. The PC can differ in size and protein content depending on the C. botulinum strain. The oral toxicity of the BoNT PC increases as the size of the PC increases, but the molecular architecture of these large complexes and how they contribute to BoNT toxicity have not been elucidated. We have generated 2D images of PCs from strains producing BoNT serotypes A1, B, and E using negative stain electron microscopy and single-particle averaging. The BoNT/A1 and BoNT/B PCs were observed as ovoid-shaped bodies with three appendages, whereas the BoNT/E PC was observed as an ovoid body. Both the BoNT/A1 and BoNT/B PCs showed significant flexibility, and the BoNT/B PC was documented as a heterogeneous population of assembly/disassembly intermediates. We have also determined 3D structures for each serotype using the random conical tilt approach. Crystal structures of the individual proteins were placed into the BoNT/A1 and BoNT/B PC electron density maps to generate unique detailed models of the BoNT PCs. The structures highlight an effective platform that can be engineered for the development of mucosal vaccines and the intestinal absorption of oral biologics. 相似文献
614.
615.
Borden EC Sen GC Uze G Silverman RH Ransohoff RM Foster GR Stark GR 《Nature reviews. Drug discovery》2007,6(12):975-990
616.
617.
Background Pre-clinical activity of SSG against melanoma and renal cancer has been identified recently although the drug’s mechanism
of action and activity against tumors of additional histological-types remain undefined.
Methods The effects of SSG and SSG combination with other agents on DU145 human prostate carcinoma xenograft tumors in mice and on
DU145 cell subpopulations of differential SSG sensitivities were evaluated.
Results DU145 tumor growth was inhibited by SSG (69%), IFNα2 (33%) or the combination (80%) that induced complete regression of WM9
human melanoma tumors. DU145 cells in culture were also partially growth inhibited by SSG at killing doses (200–800 μg/ml)
for WM9 cells, indicating a correlation of SSG inhibition of cancer cell growth in vitro and in vivo. DU145 cells formed multiple
micro tumors in mice treated with SSG or SSG/IFNα2 in contrast to the single large tumors in the control or IFNα2-treated
mice, suggesting the existence of an SSG-resistant subpopulation in DU145 cells. Indeed, DU145 but not WM9 cells formed colonies
(∼4% frequency) when cultured in the presence of SSG. Single cell clone (DU145–7) isolated from DU145 cells showed SSG-resistant
growth in culture, unassociated with cross-resistance to IFNα2 and converted to SSG-responsive cells by BSO that inhibited
intracellular glutathione levels.
Conclusions These results implicate a role for direct growth inhibition in SSG anti-tumor action, provide novel insights into the mechanism
of tumor resistance to the drug and suggest a therapeutic potential for SSG and its combinations with IFNα2 or BSO for prostate
cancer that warrants further investigation. 相似文献
618.
Powrnima Joshi Barbara Jacobs Adeeb Derakhshan Lee R. Moore Paul Elson Pierre L. Triozzi Ernest Borden Maciej Zborowski 《Oncotarget》2014,5(9):2450-2461
Circulating tumor cells have emerged as prognostic biomarkers in the treatment of metastatic cancers of epithelial origins viz., breast, colorectal and prostate. These tumors express Epithelial Cell Adhesion Molecule (EpCAM) on their cell surface which is used as an antigen for immunoaffinity capture. However, EpCAM capture technologies are of limited utility for non-epithelial cancers such as melanoma.We report a method to enrich Circulating Melanoma Cells (CMCs) that does not presuppose malignant cell characteristics. CMCs were enriched by centrifugation of blood samples from healthy (N = 10) and patient (N = 11) donors, followed by RBC lysis and immunomagnetic depletion of CD45-positive leukocytes in a specialized magnetic separator. CMCs were identified by immunocytochemistry using Melan-A or S100B as melanoma markers and enumerated using automated microscopy image analyses. Separation was optimized for maximum sensitivity and recovery of CMCs.Our results indicate large number of CMCs in Stage IV melanoma patients. Analysis of survival suggested a trend toward decreased survival with increased number of CMCs. Moreover, melanoma-associated miRs were found to be higher in CMC-enriched fractions in two patients when compared with the unseparated samples, validating this method as applicable for molecular analyses.Negative selection is a promising approach for isolation of CMCs and other EpCAM -negative CTCs, and is amenable to molecular analysis of CMCs. Further studies are required to validate its efficacy at capturing specific circulating cells for genomic analysis, and xenograft studies. 相似文献
619.
Cummings GE Voaklander D Vincenten J Policicchio C Borden K 《The Journal of emergency medicine》2000,18(3):299-303
A pilot study to survey the attitudes of emergency department (ED) personnel regarding their role in injury prevention education in children and parents was conducted at a tertiary care trauma center. The survey consisted of 14 statements, asking staff members their level of agreement (from strongly agree to strongly disagree) on a forced-choice four-point scale. These were followed by two questions asking staff members to rank schools, physician's offices, emergency departments, and public health units on their value in providing injury prevention information to children and parents. Before the intervention (an in-service training program on the importance of documenting the circumstances of injury on a patient's chart), a 50% randomly selected sample of ED staff members was asked in May 1997 to complete the survey. After the data collection prepilot (4 months later), the remaining 50% was asked in September 1997 to complete the same questionnaire. Administration of the preintervention survey resulted in 53 of 62 surveys being returned (85%). The postintervention survey was completed by 35 of the 41 staff members still eligible (85%), those who were employed in the ED during the entire pilot project. There was no statistically significant difference between the pre- and post-pilot groups on any demographic characteristics. Staff members agreed least with the statement that ED physicians and staff members could impact the severity of injuries to children by providing counseling to parents (68.1% preintervention and 64.5% postintervention agreement). Of most significance was the fact that a lower percentage of staff members agreed postintervention that almost all injuries to children were avoidable. The emergency department was the lowest ranked information dissemination venue for both parents and children. 相似文献
620.
Simon Kaja Nathalie Sumien Priscilla K. Borden Nitasha Khullar Maaz Iqbal Julie L. Collins Michael J. Forster Peter Koulen 《Age (Dordrecht, Netherlands)》2013,35(5):1799-1808
The molecular mechanisms underlying cognitive decline during healthy aging remain largely unknown. Utilizing aged wild-type C57BL/6 mice as a model for normal aging, we tested the hypothesis that cognitive performance, memory, and learning as assessed in established behavioral testing paradigms are correlated with the differential expression of isoforms of the Homer family of synaptic scaffolding proteins. Here we describe a loss of cognitive and motor function that occurs when Homer-1a/Vesl-1S protein levels drop during aging. Our data describe a novel mechanism of age-related synaptic changes contributing to loss of biological function, spatial learning, and memory formation as well as motor coordination, with the dominant negative uncoupler of synaptic protein clustering, Homer-1a/Vesl-1S, as a potential target for the prophylaxis and treatment of age-related cognitive decline.