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Biomedical subjects

A Botero

Publications and source records attributed to A Botero.

9 recordsLinked to original sources
PubMed2000

Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation.

Thioredoxin (TRX) is a cytoplasmic, redox-sensitive signaling factor believed to participate in the regulation of nuclear transcription factors mediating cellular responses to environmental stress. Activation of the activator protein (AP)-1 transcription factor is thought to be mediated in part by redox-sensitive interactions between the nuclear signaling protein redox factor-1 (Ref-1) and TRX. In this study, the role of TRX and Ref-1 in the activation of the AP-1 complex was examined in HeLa and Jurkat cell lines exposed to ionizing radiation (IR). After exposure to IR, nuclear levels of immunoreactive TRX increased, accompanied by an increase in AP-1 DNA binding activity. It was shown that a physical interaction between Ref-1 and TRX occurs within the nucleus and is enhanced after exposure to IR. Furthermore, TRX immunoprecipitated from irradiated cells was capable of activating AP-1 DNA binding activity in nonirradiated nuclear extracts. In addition, immunodepletion of Ref-1 from nuclear extracts demonstrated that the increase in AP-1 DNA binding activity after IR was also dependent upon the presence of Ref-1 from irradiated cells. Finally, the ability of both TRX and Ref-1 from irradiated cells to stimulate AP-1 DNA binding in nonirradiated nuclear extracts was abolished by chemical oxidation and restored by chemical reduction. These results indicate that, in response to IR, TRX and Ref-1 undergo changes in redox state that contribute to the activation of AP-1 DNA binding activity. These experiments suggest that a redox-sensitive signaling pathway leading from TRX to Ref-1 to the AP-1 complex participates in the up-regulation of DNA binding activity in response to ionizing radiation.

Animals↗
PubMed1999

Heat shock inhibits radiation-induced activation of NF-kappaB via inhibition of I-kappaB kinase.

Radiation stimulates signaling cascades that result in the activation of several transcription factors that are believed to play a central role in protective response(s) to ionizing radiation (IR). It is also well established that heat shock alters the regulation of signaling cascades and transcription factors and is a potent radiosensitizing agent. To explore the hypothesis that heat disrupts or alters the regulation of signaling factors activated by IR, the effect of heat shock on IR-induced activation of NF-kappaB was determined. Irradiated HeLa cells demonstrated transient increases in NF-kappaB DNA binding activity and NF-kappaB protein nuclear localization. In addition, irradiated cells demonstrated increased I-kappaB phosphorylation and decreased I-kappaBalpha cytoplasmic protein levels, corresponding temporally with the increase of NF-kappaB DNA binding. Heat shock prior to IR inhibited the increase in NF-kappaB DNA binding activity, nuclear localization of NF-kappaB, and the phosphorylation and subsequent degradation of I-kappaB. I-kappaB kinase (IKK) immunoprecipitation assays demonstrated an increase in IKK catalytic activity in response to IR that was inhibited by pretreatment with heat. Kinetic experiments determined that heat-induced inhibition of NF-kappaB activation in response to IR decayed within 5 h after heating. Furthermore, pretreatment with cycloheximide, to block de novo protein synthesis, did not alter heat shock inhibition of IR induction of NF-kappaB. These experiments demonstrate that heat shock transiently inhibits IR induction of NF-kappaB DNA binding activity by preventing IKK activation and suggests a mechanism independent of protein synthesis.

Cell Nucleus↗
PubMed1999

Intracellular oxidation/reduction status in the regulation of transcription factors NF-kappaB and AP-1.

The eukaryotic cell contains a multitude of pathways coupling environmental stimuli to the specific regulation of gene expression. Two early response transcriptional complexes, NF-kappaB and AP-1, appear to respond to environmental stressors by inducing the expression of response specific downstream genes. Both are well-characterized transcriptional regulatory factors that are induced by a wide variety of seemingly unrelated exogenous and endogenous agents and serve important roles in cell growth and differentiation, immunity, inflammation, and other preprogrammed cellular genetic processes. The activities of NF-kappaB and AP-1 are also affected following exposure to chemicals, drugs, or other agents that appear to alter the cellular oxidation/reduction (redox) status. From these observations, it has been suggested that changes in cellular oxidation/reduction status, communicated via a series of cellular redox-sensitive signaling circuitry employing metal- and thiol-containing proteins, serve as common mechanisms linking environmental stressors to adaptive cellular responses. As such, these transcription factors are ideal paradigms to study the mechanism and possible physiological significance of early response genes in the cellular response to changes in cellular redox status. In this article we summarize the evidence suggesting that cellular redox regulates these transcription factors.

Animals↗
PubMed1999

Meta-analysis of randomized controlled trials comparing laparoscopic and open appendectomy.

We performed a meta-analysis to determine whether laparoscopic or open appendectomy gives better outcomes for patients with suspected acute appendicitis. Studies were selected from the MEDLINE database, personal files, and meeting abstracts. Eleven of 21 randomized controlled trials were included in the meta-analysis. Pooled effect size estimates were calculated using a random effects model. Laparoscopic appendectomy reduced time to full functioning by 5.48 days (95% confidence interval [CI] 3.70 to 7.26; p < 0.001), improved postoperative pain at 24 hours measured by a visual analog scale from 0 to 10 by 1.19 points (95% CI -2.14 to -0.24 points; p=0.014), and decreased the absolute risk for wound infection by 3.2% (95% CI -5.6% to -0. 8%; p=0.009). Operating time was increased by 17.12 min (95% CI 14.19 to 20.03; p < 0.0001). There was no difference between the two surgeries for length of hospital stay, readmission rate, and intra-abdominal abscess formation. Laparoscopic appendectomy improves patient outcomes.

Appendectomy↗
PubMed1995

Evaluation of the technique used by health-care workers for taking blood pressure.

The precise guidelines recommended by the American Heart Association for blood pressure measurement are commonly overlooked by health-care workers, who generally take blood pressure in an arbitrary way. To validate this observation we designed a descriptive and observational study to be carried out in a major hospital. One hundred and seventy-two health-care workers divided into four groups (63 general practitioners, 25 clinical and 25 surgical specialists, and 59 nurses) were evaluated in a two-part test. In the first part (practical), the examinee had to follow all the steps recommended by the American Heart Association to get a passing score. In the second part (theoretical, which came second to avoid influencing the practical), the examinee had to answer correctly 7 of 10 questions based on the American Heart Association's guidelines to obtain a passing score. The highest accepted variation in systolic and diastolic pressures between examinee and observer was +/- 4 mm Hg. None of the examinees followed the American Heart Association's recommendations. Sixty-three percent of systolic and 53% of diastolic readings were out of range. Surgical specialists obtained the best practical results (48% systolic and 64% diastolic within range), and nurses obtained the lowest values (29% and 39%, respectively; P = .03 versus surgical specialists). These two groups showed deficiencies in the theoretical test (nurses, 10% correct answers and surgical specialists, 16%). Clinical specialists obtained the best results on the theoretical test (60% correct; P < .05 versus the other groups) but were deficient in the practical test (32% systolic and 60% diastolic within range).(ABSTRACT TRUNCATED AT 250 WORDS)

American Heart Association↗