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