Biomedical subjects

Ronald Jensen

Publications and source records attributed to Ronald Jensen.

4 recordsLinked to original sources

PubMed2005

High-resolution analysis of genomic alterations and human papillomavirus integration in anal intraepithelial neoplasia.

Anal intraepithelial neoplasia (AIN) is the likely precursor to anal cancer. AIN is associated with human papillomavirus (HPV) infection, and HPV-associated genomic instability may play an important role in the progression of squamous intraepithelial neoplasia to cancer. Microarray-based comparative genome hybridization (aCGH) was performed on DNA from AIN specimens to determine the host genomic alterations and their correlation with HPV DNA integration or rearrangement. Of 27 high-grade AIN specimens tested by CGH, 8 (30%) showed regional DNA copy number abnormalities (CNAs). Five additional cases previously identified by chromosome CGH to carry CNAs were reanalyzed by aCGH and pooled with the 8 new cases for analysis. The most common regions of gain were on chromosome arms 1p, 1q, 3q, 8p, and 20q. The most common regions of loss were on chromosome arms 2q, 7q, 11p, 11q, and 15q. HPV16 DNA integration or rearrangement correlated with CNAs in host cell DNA (P = 0.007). Although aCGH can resolve amplicons at the 1- to 2-megabase (Mb) regional resolution, the most common alteration on chromosome 3 could only be resolved to a 75-Mb region from 3q21 to qtel. Our data suggest that there may be several oncogenes in this region that are coactivated to contribute to progression to high-grade AIN.

Anus Neoplasms↗

PubMed2003

Recurrent central cord syndrome at the level of a solid cervical vertebral fusion.

STUDY DESIGN: A case of a solid cervical vertebral fusion that failed to protect against recurrent central cord syndrome at the same spinal level is described. OBJECTIVES: To alert clinicians to the potential for incomplete spinal cord lesions at the same level as cervical vertebral fusions. SUMMARY OF BACKGROUND DATA: The clinical symptomatology of central cord syndrome is discussed and the advantages of T2-weighted magnetic resonance imaging in such cases is considered. No prior reports of central cord syndrome occurring directly posterior to a solidly fused disc segment were found in the literature. METHODS: The clinical and T2-weighted magnetic resonance imaging features associated with central cord syndrome are presented. The traumatized region developed immediately posterior to the site of an anterior cervical diskectomy and uncovertebral osteophytectomy between the fourth and fifth cervical vertebrae with bone grafting that had been performed more than 3 years earlier. RESULTS: Symptoms of the central cord syndrome resolved over the course of 4 months with no other intervention other than the use of a Philadelphia cervical collar. Five years later, the patient remained symptom free. CONCLUSION: This case illustrates that clinicians must be aware of the potential occurrence of central cord syndrome in patients with solidly fused cervical segments, and that cervical fusion does not necessarily protect against future incomplete spinal cord injury, such as central cord syndrome, at the level of the fusion.

Adult↗

PubMed2003

Optimizing stringency for expression microarrays.

While several studies have reported methods to optimize expression microarray protocols, none have dealt directly with hybridization wash stringency. We designed a series of experiments to determine the optimal stringency conditions for microarray experiments, using reproducibility and magnitudes of log2 (test/reference) ratio values as measures of quality. Low-stringency wash conditions of cell line hybridizations led to nonspecific binding, resulting in increased intensities, decreased magnitude of ratios, and poor reproducibility. Relatively high-stringency wash conditions were found to give the best reproducibility and large magnitude ratio changes, although increasing the stringency beyond this point led to lower magnitude ratios and poorer reproducibility. The expression levels of the ERBB2 oncogene in the BT474 versus MCF7 cell lines showed that high-stringency wash conditions gave the best agreement with real-time quantitative PCR, although the magnitude of the changes by microarray was smaller than for real-time quantitative PCR. Analysis of a series of cell lines washed at the optimized stringency indicated that the rank order of relative expression levels for ERBB2 microarray clones agreed well with the rank order of ERBB2 levels, as measured by quantitative PCR. These results indicate that the optimization of stringency conditions will improve microarray reproducibility and give more representative expression values.

Artifacts↗

PubMedDate not supplied

Proteome and transcriptome analysis of retinoic acid-induced differentiation of human acute promyelocytic leukemia cells, NB4.

Acute promyelocytic leukemia (APL) is characterized by a translocation t(15:17) that fuses the retinoic acid receptor gene with the promyelocytic gene, which blocks differentiation to normal granulocytes. NB4 cells, derived from human acute promyelocytic leukemia, display this genotype and phenotype. All trans-retinoic acid (ATRA) induces differentiation of NB4 cell cultures in vitro and APL in vivo, although resistance to differentiation therapy frequently develops. To identify genes involved in differentiation, we compared gene expression at the mRNA and protein levels using microarray analyses and two-dimensional (2D) difference gel electrophoresis (DIGE), plus MALDI-TOF-TOF mass spectrometry. Differentially expressed transcripts were identified using oligonucleotide-based microarrays with targets representing almost 14 000 genes. Real time PCR was performed on a subset of genes whose products were shown to be differentially expressed using proteomic and/or genomic approaches. Our analyses identified 46 genes that were differentially expressed in NB4 +/- ATRA; 22 were identified using 2D-DIGE and 24 using microarray analysis. All but four of these genes were expressed at higher levels in differentiated cells, and several controlled cell structure (internal and cytoskelatal) or signal transduction. We observed that proteome analysis with DIGE and silver-stained 2D gel electrophoresis analyses revealed significant differences between the two measurement approaches. Furthermore, our data showed significant discordance between gene expression at the protein and transcript levels.

Cell Differentiation↗