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Structure and function of chromatin : studies at the nucleosome and nuclear matrix levels
Several levels of eukaryotic chromatin structure have
been observed: the nucleosome, the 10 nm and 30 nm fibers
and loop domains, apparently attached to the nuclear
matrix. In this research, the structure and function of
chromatin at two of these levels was investigated, with
studies on both nucleosome positioning and chromatin
interaction with the nuclear matrix.
In some instances, it seems that nucleosome
positioning on genes is not random. Although no simple,
definitive "nucleosome binding" sequences can be found
which explicitly determine nucleosome positions, it is of
interest to note that periodicity of some degenerate
groupings of dinucleotides and of maximum bendability are
correlated in nucleosomal DNA sequences. This research
supports the proposition that nucleosome positioning on DNA
may depend on the existence of periodic regularities in DNA
bendability. It also indicates that information contained
within local sequences, determine properties which affect
the differential propensity for positioning of nucleosomes.
Bendability seems to represent at least one of the major
sequence-directed structural constraints on the ability of
any particular stretch of DNA to form nucleosomes.
Studies of the nucleosome spacing in the 5' flanking
region of the chicken beta globin gene and coding sequence
of the chicken thymidine kinase gene in chicken erythrocyte
cells and chicken embryo myoblast cells demonstrate that
the nucleosome spacing in these regions is most likely cell
type-dependent, rather than gene dependent; and probably
reflects a general effect of the special histone, H5,
carried in erythrocyte cells.
DNA loops are proposed to be anchored to the nuclear
matrix, which may be involved in DNA replication and
repair, RNA transcription and processing, hormone action,
virus infection, and carcinogenesis. Studies of the
relationship between gene activity and nuclear matrix
association, have given both positive and negative results
with the chicken thymidine kinase gene, the beta-globin
gene and the mouse dihydrofolate reductase gene. There
appears to be no simple correlation between nuclear matrix
association and gene transcriptional activity. The working
hypothesis developed here is that the apparent association
of specific genes with the nuclear matrix is mainly caused
by specific DNA binding proteins which partition in the
nuclear matrix fraction.
Adenovirus was used as a model to investigate the role
which the nuclear matrix may play in virus infection and
viral DNA replication. The origins of replication of
adenovirus DNA are found to be strongly associated with the
nuclear matrix. One of the nuclear matrix proteins, of
mass 140 KD, has been found from a UV cross-linking
experiment to be able to bind specifically with the origins
of replication of adenovirus. However, whether these
proteins are in vivo components of the nuclear matrix or
that their association is an artifact of the isolation,
could not be determined with certainty
Primary appendiceal mucinous adenocarcinoma in two first-degree relatives: case report and review
Carcinomas of the appendix are exceedingly rare tumors and have an annual age-adjusted incidence of around 0.4 cases per 100,000. Appendiceal adenocarcinoma accounts for < 0.5% of all gastrointestinal neoplasms and, of these, mucinous adenocarcinomas account for the majority. Published accounts of familial instances of primary appendiceal tumors are strikingly rare. We report two siblings who both developed primary mucinous adenocarcinomas. A genetics evaluation was conducted to determine if there was a recognizable underlying single gene disorder; no DNA mismatch repair defect was evident, and no other diagnosis was apparent. A review of appendiceal cancers seen at Mayo Clinic from l997 to the present was conducted to search for additional familial cases. Among 316 cases of primary appendiceal cancer of any histologic type, this sib pair was the only family reporting a second affected family member. The occurrence of appendiceal cancer in siblings may represent a random occurrence. An exceedingly rare predisposition syndrome cannot be ruled out
Comparison of the Commercial Color LCD and the Medical Monochrome LCD Using Randomized Object Test Patterns
Workstations and electronic display devices in a picture archiving and communication system (PACS) provide a convenient and efficient platform for medical diagnosis. The performance of display devices has to be verified to ensure that image quality is not degraded. In this study, we designed a set of randomized object test patterns (ROTPs) consisting of randomly located spheres with various image characteristics to evaluate the performance of a 2.5 mega-pixel (MP) commercial color LCD and a 3 MP diagnostic monochrome LCD in several aspects, including the contrast, resolution, point spread effect, and noise. The ROTPs were then merged into 120 abdominal CT images. Five radiologists were invited to review the CT images, and receiver operating characteristic (ROC) analysis was carried out using a five-point rating scale. In the high background patterns of ROTPs, the sensitivity performance was comparable between both monitors in terms of contrast and resolution, whereas, in the low background patterns, the performance of the commercial color LCD was significantly poorer than that of the diagnostic monochrome LCD in all aspects. The average area under the ROC curve (AUC) for reviewing abdominal CT images was 0.717±0.0200 and 0.740±0.0195 for the color monitor and the diagnostic monitor, respectively. The observation time (OT) was 145±27.6 min and 127±19.3 min, respectively. No significant differences appeared in AUC (p = 0.265) and OT (p = 0.07). The overall results indicate that ROTPs can be implemented as a quality control tool to evaluate the intrinsic characteristics of display devices. Although there is still a gap in technology between different types of LCDs, commercial color LCDs could replace diagnostic monochrome LCDs as a platform for reviewing abdominal CT images after monitor calibration
The inflammatory microenvironment in colorectal neoplasia
Peer reviewedPublisher PD
The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic Target for Radiation Sensitization in Lung Cancer
Elucidating the mechanism of over and under expression of proteins is critical in developing a better understanding of cancer. Multiple techniques are used to examine differential expression of proteins in cells and assess changes in protein expression in response to therapies such as radiation. Reduced expression can be caused by protein inactivation, mRNA instability, or reduced transcription. The following protocol was used to determine the mechanism for the reduced expression of an antiapoptotic factor, survivin, in normal tissues in response to radiation and the defect in cancer cells that prevents this reduction. We also examined ways to overcome survivin over expression in cancer cells in order to sensitize them to radiation. We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes
Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study
Data acquisition and analyses were funded by Teva Pharmaceuticals
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