Biomedical subjects

David Hernandez

Publications and source records attributed to David Hernandez.

4 recordsLinked to original sources

PubMed2005

Conserved transcription factor binding sites of cancer markers derived from primary lung adenocarcinoma microarrays.

Gene transcription in a set of 49 human primary lung adenocarcinomas and 9 normal lung tissue samples was examined using Affymetrix GeneChip technology. A total of 3442 genes, called the set M AD, were found to be either up- or down-regulated by at least 2-fold between the two phenotypes. Genes assigned to a particular gene ontology term were found, in many cases, to be significantly unevenly distributed between the genes in and outside M AD. Terms that were overrepresented in M AD included functions directly implicated in the cancer cell metabolism. Based on their functional roles and expression profiles, genes in M AD were grouped into likely co-regulated gene sets. Highly conserved sequences in the 5 kb region upstream of the genes in these sets were identified with the motif discovery tool, MoDEL. Potential oncogenic transcription factors and their corresponding binding sites were identified in these conserved regions using the TRANSFAC 8.3 database. Several of the transcription factors identified in this study have been shown elsewhere to be involved in oncogenic processes. This study searched beyond phenotypic gene expression profiles in cancer cells, in order to identify the more important regulatory transcription factors that caused these aberrations in gene expression.

5' Flanking Region↗

PubMed2004

MoDEL: an efficient strategy for ungapped local multiple alignment.

We introduce a method for ungapped local multiple alignment (ULMA) in a given set of amino acid or nucleotide sequences. This method explores two search spaces using a linked optimization strategy. The first search space M consists of all possible words of a given length W, defined on the residue alphabet. An evolutionary algorithm searches this space globally. The second search space P consists of all possible ULMAs in the sequence set, each ULMA being represented by a position vector defining exactly one subsequence of length W per sequence. This search space is sampled with hill-climbing processes. The search of both spaces are coupled by projecting high scoring results from the global evolutionary search of M onto P. The hill-climbing processes then refine the optimization by local search, using the relative entropy between the ULMA and background residue frequencies as an objective function. We demonstrate some advantages of our strategy by analyzing difficult natural amino acid sequences and artificial datasets. A web interface is available at

Algorithms↗

PubMed2004

Positive proximal (bladder neck) margin at radical prostatectomy confers greater risk of biochemical progression.

OBJECTIVES: To identify the prognostic significance of positive bladder neck margin as the sole positive margin after radical retropubic prostatectomy for treatment of prostate cancer. METHODS: We retrospectively analyzed the data from patients who underwent radical retropubic prostatectomy at Johns Hopkins Hospital between 1984 and 2001. Of 164 patients with positive margins, 38 had a positive margin only at the bladder neck margin and 126 had a positive margin at one or more locations separate from the bladder neck margin. RESULTS: Kaplan-Meier analyses showed that patients with a positive bladder neck margin had a greater biochemical progression risk than patients with positive margins at one or more locations other than the bladder neck margin. The 5-year actuarial risk of progression in men with positive and negative bladder neck margins was 69.8% and 33.0%, respectively. A positive bladder neck margin was statistically an independently significant predictor of progression (P = 0.001), along with the prostatectomy Gleason score (P = 0.0001) in the multivariate analysis. The hazard ratio for predicting progression for postoperative Gleason score and bladder neck positivity was 2.1 and 2.5, respectively. Serum prostate-specific antigen values, clinical stage, age, and the percentage of tumor at the bladder neck margin were not predictors of progression in either univariate or multivariate analysis. CONCLUSIONS: Patients with a positive bladder neck margin as the sole positive margin at radical retropubic prostatectomy have a greater risk of biochemical progression than patients with one or more positive margins at other locations, although not as adverse as the risk reported for those with Stage T4 disease.

Adenocarcinoma↗

PubMed2002

Regulation and mode of action of the second small RNA activator of RpoS translation, RprA.

Translation of the stationary phase sigma factor RpoS is stimulated by at least two small RNAs, DsrA and RprA. DsrA disrupts an inhibitory secondary structure in the rpoS leader mRNA by pairing with the upstream RNA. Mutations in rprA and compensating mutations in the rpoS leader demonstrate that RprA interacts with the same region of the RpoS leader as DsrA. This is the first example of two different small RNAs regulating a common target. Regulation of these RNAs differs. DsrA synthesis is increased at low temperature. We find that RprA synthesis is regulated by the RcsC/RcsB phosphorelay system, previously found to regulate capsule synthesis and promoters of ftsZ and osmC. An rcsB null mutation abolishes the basal level, whereas mutations in rcsC that activate capsule synthesis also activate expression of the rprA promoter. An essential site with similarity to other RcsB-regulated promoters was defined in the rprA promoter. Activation of the RcsC/RcsB system leads to increased RpoS synthesis, in an RprA-dependent fashion. This work suggests a new signal for RpoS translation and extends the global regulation effected by the RcsC/RcsB system to coregulation of RpoS with capsule and FtsZ.

Bacterial Proteins↗