PubMed Health⌕ Search

Biomedical subjects

J P Carson

Publications and source records attributed to J P Carson.

8 recordsLinked to original sources

A method for automated detection of gene expression required for the establishment of a digital transcriptome-wide gene expression atlas.

Acquiring information about the expression of a gene in different cell populations and tissues can provide key insight into the function of the gene. A high-throughput in situ hybridization (ISH) method was recently developed for rapid and reproducible acquisition of gene expression patterns in serial tissue sections at cellular resolution. Characterizing and analysing expression patterns on thousands of sections requires efficient methods for locating cells and estimating the level of expression in each cell. Such cellular quantification is an essential step in both annotating and quantitatively comparing high-throughput ISH results. Here we describe a novel automated and efficient methodology for performing this quantification on postnatal mouse brain.

Animals↗

Tumor necrosis factor alpha induces BID cleavage and bypasses antiapoptotic signals in prostate cancer LNCaP cells.

Survival of cancer cells in response to therapy, immune response, or metastasis depends on interactions between pro- and antiapoptotic signals. Two major proapoptotic pathways have been described: (a) a death receptor pathway; and (b) a mitochondrial pathway. We reported previously that Akt and the epidermal growth factor (EGF) receptor send separate, redundant survival signals that act to inhibit the mitochondrial proapoptotic pathway in prostate cancer LNCaP cells. However, it was unclear at what level the pro- and antiapoptotic signals interact in these cells, and it was also unclear whether these signals would inhibit the death receptor pathway. We found that EGF can protect LNCaP cells from apoptosis induced by LY294002 but not from tumor necrosis factor a (TNF-alpha)-induced apoptosis. Furthermore, TNF-alpha induced apoptosis under conditions in which Akt was active. Treatment with TNF-alpha resulted in activation of caspase 8 and cleavage of BID, which in turn induced cytochrome c release and caspase 9-dependent activation of effector caspases. Thus, proapoptotic signals induced by both TNF-alpha and LY294002 converge on mitochondria and trigger cytochrome c release. Because EGF can inhibit cytochrome c release induced by LY294002 but not cytochrome c release induced by TNF-alpha, we suggest that the EGF survival mechanism operates on the mitochondrial pathway at a site upstream of cytochrome c release. The ability of TNF-alpha to bypass survival signals from activated EGF receptor and Akt in prostate cancer cells makes death receptor signaling a promising avenue for therapeutic intervention.

Apoptosis↗

Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B.

Constitutive activation of the phosphatidylinositol 3'-kinase (PI3 kinase)-Akt/protein kinase B (PKB) "survival signaling" pathway is a likely mechanism by which many cancers become refractory to cytotoxic therapy. In LNCaP prostate cancer cells, the PTEN phosphoinositide phosphatase is inactivated, leading to constitutive activation of Akt/PKB and resistance to apoptosis. However, apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment with PI3 kinase inhibitors. Surprisingly, androgen, epidermal growth factor, or serum can protect these cells from apoptosis, even in the presence of PI3 kinase inhibitors and without activation of Akt/PKB, indicating the activity of a novel, Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level prior to caspase 3 activation and release of cytochrome c from mitochondria.

Apoptosis↗

Special protocols for patients with trauma.

The ED care of the patient with trauma can be facilitated by the establishment of protocols to ensure prompt access to lifesaving and limb-saving procedures and care. Specific protocols for patients with trauma support assessment and treatment in both the emergency and long-term phases of care.

Clinical Protocols↗

Anatomy of the accident scene: a prospective study of injury and mortality.

This study of the accident scene focuses on the effects of vehicular deformity and restraint devices on occupant injury. In 500 patients evaluated in a Level I trauma center, seatbelts significantly reduced the likelihood of individuals' requiring the trauma center (P less than 0.0001). Seatbelts also significantly reduced the mortality rate of those who were transported to the trauma center (P less than 0.04). Dashboard intrusion correlated with pelvic (P less than 0.001) and femur (P less than 0.03) fractures, closed head injuries (P less than 0.001), and intraabdominal injuries (P less than 0.02). Steering wheel deformity correlated with pelvic fractures (P less than 0.001) and closed head injuries (P less than 0.005). Windshield violation correlated with closed head injuries (P less than 0.014) and spinal fractures (P less than 0.03). Irreparable vehicles correlated with pelvic (P less than 0.0001) and femur fractures (P less than 0.01), closed head injuries (P less than 0.0001) and intra-abdominal injuries (P less than 0.0001). The authors conclude that a careful examination of the accident scene for specific mechanisms of injury can lead to better prehospital care, more rapid and consistent diagnosis of injury, and improved patient outcome. Further prospective studies should accumulate data that will improve prehospital care, alert physicians to possible injury, increase community awareness of injury prevention, and improve vehicle construction.

Accidents, Traffic↗

Pott's puffy tumor, frontal sinusitis, frontal bone osteomyelitis, and epidural abscess secondary to a wrestling injury.

A blow sustained to the head while wrestling may produce frontal osteomyelitis and its complications, Pott's puffy tumor and epidural abscess. The symptoms may be minimal and may be manifested only by a mild headache and occasional stuffy nose. A 16-year-old boy was studied one month after a head injury sustained while wrestling, complaining only of recurrent headaches and fever. A fluctuant mass was found in the midfrontal area. Frontal sinusitis, subperiosteal abscesss epidural abscess, and frontal osteomyelitis were found at surgery. The frontal bone involved by the osteomyelitis was debrided, and the epidural abscess was evacuated.

Adolescent↗