Search PubMed⌕ Search

Biomedical subjects

J Perren Cobb

Publications and source records attributed to J Perren Cobb.

23 records · Page 2Linked to original sources
PubMed2004

Gene expression profiles of livers from thermally injured rats.

The liver plays an important role in a severe thermal injury by modulating immune function, inflammatory processes and the acute phase response, which are an orchestrated attempt to restore homeostasis. Using high-density oligonucleotide arrays, we examined the gene expression profile in the livers of rats between 2 and 240 h after a 40% total body surface area (TBSA) burn. Alterations in gene expression unique to a thermal injury were identified. Approximately 39 genes out of 8700 genes on each array across all the time points showed a significant change in expression patterns. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses verified significant changes in early growth response-1 (Egr-1) messenger RNA (mRNA) and protein levels corresponding to the array data. Significant increases in serum levels of alpha-2-macroglobulin that correspond to changes in its mRNA levels were observed at 6 and 24 h after burn, p<0.05. The genomic pattern for liver in the hypermetabolic phase after the burn injury involves transcription factors, stress and inflammatory responses, cytoskeletal and extracellular matrix modifications, and regulation of cell proliferation and differentiation. During the initial phase of thermal injury gene expression profiles in the liver may provide some insight into how cellular protection mechanisms and systemic hypermetabolism are initiated and controlled. The genome wide changes observed may provide a rational therapeutic strategy to improve burn care.

Animals↗
PubMed2004

Sequence makes a difference: paradoxical effects of stress in vivo.

In vitro studies have shown that induction of heat shock before an inflammatory stimulus is cytoprotective, whereas induction of heat shock after an inflammatory stimulus can lead to apoptosis (the "heat shock paradox"). We sought to determine whether induction of the heat shock response in vivo caused similar, order-dependent effects on survival, and if so, by what mechanism. ND4 and C57BL/6 mice were used to calibrate the response to hyperthermia at 41.5 degrees C via induction of inducible heat shock protein 70. Sequences of heat shock and septic stresses were studied in murine models of hyperthermia (41.5 degrees C for 20 min) and cecal ligation and puncture (CLP), respectively. Previous heat shock to 41.5 degrees C did not protect CLP mice when compared with control CLP animals heated to 37 degrees C, but heat shock increased mortality when activated after CLP compared with controls. This effect of heat shock on CLP mortality was strain independent, and did not involve alterations in CLP-induced thymus, spleen, or intestinal apoptosis. We conclude that the heat shock paradox can occur in vitro and in vivo, and that the negative effects of heat shock on survival after CLP appeared to be strain independent. Furthermore, the stress of general anesthesia and warming also altered CLP mortality unexpectedly. The cellular mechanisms responsible for these "stressor" paradoxes in vivo are not known, but do not involve altered sepsis-induced apoptosis.

Animals↗
PubMed2002

Depletion of dendritic cells, but not macrophages, in patients with sepsis.

Dendritic cells (DCs) are a group of APCs that have an extraordinary capacity to interact with T and B cells and modulate their responses to invading pathogens. Although a number of defects in the immune system have been identified in sepsis, few studies have examined the effect of sepsis on DCs, which is the purpose of this study. In addition, this study investigated the effect of sepsis on macrophages, which are reported to undergo apoptosis, and MHC II expression, which has been noted to be decreased in sepsis. Spleens from 26 septic patients and 20 trauma patients were evaluated by immunohistochemical staining. Although sepsis did not decrease the number of macrophages, sepsis did cause a dramatic reduction in the percentage area of spleen occupied by FDCs, i.e., 2.9 +/- 0.4 vs 0.7 +/- 0.2% in trauma and septic patients, respectively. The number of MHC II-expressing cells, including interdigitating DCs, was decreased in septic, compared with trauma, patients. However, sepsis did not appear to induce a loss of MHC II expression in those B cells, macrophages, or DCs that were still present. The dramatic loss of DCs in sepsis may significantly impair B and T cell function and contribute to the immune suppression that is a hallmark of the disorder.

Adolescent↗
PubMed2002

Sepsis gene expression profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays.

OBJECTIVE: DNA microarrays allow genome-wide assessment of changes in relative messenger RNA abundance and thus can be used to monitor changes in gene expression. The aim of this series of experiments was to gain experience in sepsis gene expression profiling in a well-accepted model of murine polymicrobial abdominal sepsis and begin characterizing (in the parlance of genomics) the sepsis "transcriptome." DESIGN: Prospective animal study. SETTING: University-based animal research facility.SUBJECTS C57BL/6 mice. INTERVENTIONS: After induction of general anesthesia, cecal ligation and puncture were performed to induce peritonitis and polymicrobial sepsis. The control group had sham laparotomy only. Three samples of spleen and liver were collected from septic and sham animals at 24 hrs after laparotomy. Changes in expression were measured for 588 annotated mouse genes by using a commercially available complementary DNA microarray kit. MEASUREMENTS AND MAIN RESULTS: Broad-scale gene expression profiles were characterized for septic liver and spleen and compared with sham controls. The analytical tools used included commercially available software packages and a novel analysis program. Very little overlap was observed in the septic gene expression profiles of these two organs. Most of the genes identified have previously been linked to regulation of the inflammatory response; importantly, however, some have not. In addition, hierarchical cluster analysis showed that cecal ligation and puncture at 24 hrs induced coordinate expression of genes that alter cell signaling and survival pathways in spleen, consistent with previously published reports of sepsis-induced splenocyte apoptosis. The current limitations of microarray analysis as reflected in these studies are also discussed. CONCLUSIONS: Microarray technology provides a powerful new tool for rapidly analyzing tissue-specific changes in gene expression induced by sepsis in animal models. To our knowledge, these data constitute the first report on the use of microarrays to determine the sepsis transcriptome.

Animals↗