Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA damage results from a wide variety of external agents such as chemicals and radiation. The consequences of exposure to agents that damage DNA have been traditionally studied from the perspective of cell survival and mutagenesis. Mutations are late endpoints of DNA damage. Cells respond to the earlier stages of DNA damage by inducing the expression of several genes, including those specific of the nature of the lesion. These early transcriptional responses are likely to predetermine the later fate of the damaged cell. Genes activated during this early response include those involved in DNA repair, replication, and growth control. We are interested in the transcriptional mechanisms by which cells respond to DNA damaging agents. To facilitate the measurement of gene induction, we used seven different reporter constructs integrated stably into the RKO cell line derived from a human colon carcinoma. These constructs were derived from promoters and/or response elements isolated from genes associated with DNA damage responses in human cells, and were fused to the bacterial reporter gene, choramphenicol acetyl transferase (CAT). The cell lines generated in this manner contain the promoters and/or response elements representing DNA polymerase beta, p53, gadd (growth arrest and DNA damage) 45 and 153, c-fos, TPA response element, and tissue-type plasminogen activator. These recombinant cell lines were assembled in a 96-well microtiter plate permitting their simultaneous exposure to compounds and subsequent CAT protein measurement. This assembly has been designated the CAT-Tox (D) assay. These cell lines were exposed to different classes of DNA damaging agents including those which covalently join bases to form dimers (e.g., UVC irradiation), generate DNA adducts by alkylation (e.g., methylmethane sulfonate [MMS], ethylmethane sulfonate [EMS], N-methyl-N-nitro-N-nitrosoguanine [MNNG], dimethylnitrosamine [DMN]), cross-link DNA (e.g., mitomycin C), and inhibit DNA replication by intercalative (e.g., actinomycin D) and nonintercalative (e.g., hydroxyurea) mechanisms. The transcriptional responses were measured as a function of the accumulation of CAT protein using antibodies against CAT protein in a standard ELISA. Endogenous cellular responses were evaluated for a number of the genes represented in the assay at both the mRNA and protein levels by Northern and Western blot analysis, respectively. These data corroborate the stress-induced responses measured by CAT ELISA in the CAT-Tox (D) assay, demonstrating the usefulness of this assay as a rapid and sensitive method for detection of DNA damaging agents in human cells.
 ...
PMID:Stress responses to DNA damaging agents in the human colon carcinoma cell line, RKO. 895 Mar 45

In this study we investigated the factors associated with pre-hospital delay to treat acute ischemic stroke and transient attack with intravenous recombinant tissue-plasminogen activator (rt-PA) in Japan. In 625 patients, we investigated the pathways and times of their arrival to our hospital, and the significant and independent factors in the patients' clinical backgrounds associated with delayed arrival (>2 h after notice). In total, 287 patients arrived at our hospital directly via EMS, 113 came by themselves, and 225 transferred from other institutes. Delayed arrivals occurred in 423 patients (68%). Multivariate analyses showed that staying in another hospital at notice, a worsened course, and referral from other institutes were positively related, and evening onset, having a witness at onset, loss of consciousness, and using EMS were negatively related to delayed arrival; a worsened course was positively related, and staying in other hospital at notice, having a witness at onset, loss of consciousness, and a high NIHSS on admission were negatively related to delayed alert; hypercholesterolemia and onset in a nursing home were positively related, and staying in other hospital at notice, loss of consciousness, and a high NIHSS on admission were negatively related to not using EMS. A lack of knowledge concerning stroke emergency by medical staff as well as the general public may be responsible for some stroke patients losing the chance for rt-PA treatment.
 ...
PMID:Pre-hospital delay in the use of intravenous rt-PA for acute ischemic stroke in Japan. 1839 54

Acute ischemic stroke (AIS) and its care is currently one of the most dynamic and evolving illnesses across the globe. Among the most crucial factors in providing the best care to patients are the expedient delivery of thrombolytics and endovascular intervention when indicated. Here, we review our unique model of efficient care centered in our innovative Neurological Emergency Department (Neuro ED). The Neuro ED acts as our hub for EMS communication, imaging, administration of intravenous alteplase, and transition to the Neurointerventional OR. Our structure with its enabling of shortened IV alteplase delivery times and faster door-to-needle (DTN) times may serve as an international model for stroke centers.
 ...
PMID:Innovations in Care Delivery of Stroke from Emergency Medical Services to the Neurointerventional Operating Room. 3119 27