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Biomedical subjects

D Dominguez

Publications and source records attributed to D Dominguez.

14 recordsLinked to original sources

Effect of proinflammatory cytokines (IL-6, TNF-alpha, IL-1beta) on hemodynamic performance during orthotopic liver transplantation.

BACKGROUND: Proinflammatory cytokines (IL-6, IL-1beta, TNF-alpha) released during liver transplantation may affect hemodynamic stability. The aim of the present study was to analyze the association between IL-6, TNF-alpha, and IL-1beta and systemic vascular resistance during the phases of liver transplantation. MATERIAL AND METHODS: The proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha were analyzed in the blood of 20 consecutive patients who underwent transplantation. Blood samples were drawn from the pulmonary artery at serial times during surgery. Hemodynamic parameters were determined using a cardiac output monitor. Correlations between parameters were analyzed using the Spearman's rho and Kendall's tau-b methods. RESULTS: Both in the vena cava and the pulmonary artery, significant association was observed between basal values of IL-6 during hepatectomy and systemic vascular resistance during the phases of liver transplantation: hepatectomy phase (r=.76, P=.02), anhepatic phase (r=.78, P=.03) and reperfusion phase (r=.87, P=.005). CONCLUSIONS: Basal values of IL-6 may be considered a prognostic factor for hemodynamic performance during the phases of liver transplantation.

Biomarkers↗

Structural and functional similarities between the central eukaryotic initiation factor (eIF)4A-binding domain of mammalian eIF4G and the eIF4A-binding domain of yeast eIF4G.

The translation eukaryotic initiation factor (eIF)4G of the yeast Saccharomyces cerevisiae interacts with the RNA helicase eIF4A (a member of the DEAD-box protein family; where DEAD corresponds to Asp-Glu-Ala-Asp) through a C-terminal domain in eIF4G (amino acids 542-883). Mammalian eIF4G has two interaction domains for eIF4A, a central domain and a domain close to the C-terminus. This raises the question of whether eIF4A binding to eIF4G is conserved between yeast and mammalian cells or whether it is different. We isolated eIF4G1 mutants defective in eIF4A binding and showed that these mutants are strongly impaired in translation and growth. Extracts from mutants displaying a temperature-sensitive phenotype for growth have low in vitro translation activity, which can be restored by addition of the purified eIF4G1-eIF4E complex, but not by eIF4E alone. Analysis of mutant eIF4G(542-883) proteins defective in eIF4A binding shows that the interaction of yeast eIF4A with eIF4G1 depends on amino acid motifs that are conserved between the yeast eIF4A-binding site and the central eIF4A-binding domain of mammalian eIF4G. We show that mammalian eIF4A binds tightly to yeast eIF4G1 and, furthermore, that mutant yeast eIF4G(542-883) proteins, which do not bind yeast eIF4A, do not interact with mammalian eIF4A. Despite the conservation of the eIF4A-binding site in eIF4G and the strong sequence conservation between yeast and mammalian eIF4A (66% identity; 82% similarity at the amino acid level) mammalian eIF4A does not substitute for the yeast factor in vivo and is not functional in a yeast in vitro translation system.

Amino Acid Sequence↗

Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells.

Loss of functional adenomatous polyposis coli (APC) protein results in the stabilization of cytosolic beta-catenin and activation of genes that are responsive to Lef/Tcf family transcription factors. We have recently shown that an independent cell adhesion and integrin linked kinase (ILK)-dependent pathway can also activate beta-catenin/LEF mediated gene transcription and downregulate E-cadherin expression. In addition, ILK activity and expression are elevated in adenomatous polyposis and colon carcinomas. To examine the role of this pathway in the background of APC mutations we inhibited ILK activity in APC-/- human colon carcinoma cell lines. In all cases, inhibition of ILK resulted in substantial inhibition of TCF mediated gene transcription and inhibition of transcription and expression of the TCF regulated gene, cyclin D1. Inhibition of ILK resulted in decreased nuclear beta-catenin expression, and in the inhibition of phosphorylation of GSK-3 and stimulation of its activity, leading to accelerated degradation of beta-catenin. In addition, inhibition of ILK suppressed cell growth in culture as well as growth of human colon carcinoma cells in SCID mice. Strikingly, inhibition of ILK also resulted in the transcriptional stimulation of E-cadherin expression and correlated with the inhibition of gene transcription of snail, a repressor of E-cadherin gene expression. Overexpression of ILK caused a stimulation of expression of snail, but snail expression was found not to be regulated by beta-catenin/Tcf. These data demonstrate that ILK can regulate beta-catenin/TCF and snail transcription factors by distinct pathways. We propose that inhibition of ILK may be a useful strategy in the control of progression of colon as well as other carcinomas. Oncogene (2001) 20, 133 - 140.

Adenomatous Polyposis Coli↗

Shunting is a translation strategy used by plant pararetroviruses (Caulimoviridae).

In eukaryotes standard initiation of translation involved 40S ribosome scanning to bridge the distance from the cap to the initiation codon. Recently deviations from that rule had been described, including "internal initiation", "poly-A dependent translation", and "ribosome shunting". In ribosome shunting, ribosomes start scanning at the cap but large portions of the leader are skipped. Thereby the secondary structure of the shunted region is preserved. Scanning in plant caulimoviruses involve a small open reading frame properly spaced in front of a strong stem structure, and, in order to function, the small open reading frome has to be translated and the peptide released. This arrangement can be mimicked by artificial small open reading frames and stem structures. Shunting with viral and synthetic leaders occurs not only in plant-, but also in mammalian and yeast systems. Thus it responds to an intrinsic property of the eukaryotic translational machinery and probably acts in many cases where coding regions are preceded by complex leaders.

Caulimovirus↗

Intramolecular

2-Propynyldiarylacetylenes undergo thermal intramolecular [4 + 2] cycloaddition to give benzo[b]fluorene derivatives in good yields. The hybridization of the tether connecting the reacting alkynes has a pronounced effect on the course of the reaction. Theoretical calculations and isotopic labeling studies support a mechanism which involves the generation of a cyclic allene intermediate that evolves to the final benzo[b]fluorene.

Journal Article↗

Interaction of translation initiation factor eIF4G with eIF4A in the yeast Saccharomyces cerevisiae.

Eukaryotic initiation factor (eIF) 4A is an essential protein that, in conjunction with eIF4B, catalyzes the ATP-dependent melting of RNA secondary structure in the 5'-untranslated region of mRNA during translation initiation. In higher eukaryotes, eIF4A is assumed to be recruited to the mRNA through its interaction with eIF4G. However, the failure to detect this interaction in yeast brought into question the generality of this model. The work presented here demonstrates that yeast eIF4G interacts with eIF4A both in vivo and in vitro. The eIF4A-binding site was mapped to amino acids 542-883 of yeast eIF4G1. Expression in yeast cells of the eIF4G1 domain that binds eIF4A results in cell growth inhibition, and addition of this domain to an eIF4A-dependent in vitro system inhibits translation in a dose-dependent manner. Both in vitro translation and cell growth can be specifically restored by increasing the eIF4A concentration. These data demonstrate that yeast eIF4A and eIF4G interact and suggest that this interaction is required for translation and cell growth.

Eukaryotic Initiation Factor-4A↗

Difference between observed and predicted length of stay as an indicator of inpatient care inefficiency.

OBJECTIVES: To evaluate the performance of the difference between observed and predicted length of stay (OLOS-PLOS) as an inefficiency of care indicator for inpatients. SETTING: The Internal Medicine and the General Surgery departments of Hermanos Ameijeiras Hospital in Havana. DESIGN AND STUDY PARTICIPANTS: Two sets of clinical histories were needed for each department: one for deriving the predictive equation and another to validate it. The equation was a linear multiple regression model which included variables recognized as affecting length of stay. The validation group of histories was thoroughly examined and separated into two groups: (i) adequate efficiency or mild problems and (ii) inefficiencies considered to be moderate or severe. This classification was the gold standard to obtain a receiver operating characteristic (ROC) curve for the indicator. RESULTS: The function explained 41% of the total variation for Internal Medicine and 70% for General Surgery. The indicator's mean difference between the two validation groups of histories was around 10 days for both departments. The areas under the ROC curve were 0.80 for Internal Medicine and 0.88 for General Surgery. Sensitivity and specificity > 0.7 for detecting inefficiencies of care are achieved with a cut off point of 2 days for Internal Medicine and 1 day for General Surgery. CONCLUSIONS: The use of predictive equations might be quite useful for detecting efficiency problems in inpatient health care.

Cuba↗

Plant ribosome shunting in vitro.

It has been proposed that cauliflower mosaic virus 35S RNA with its 600 nt long leader uses an unusual translation process (the translational shunt). A wheat germ in vitro translation assay was used to improve the study of this mechanism. Deletions, the introduction of stable stem-loop structures, and the inhibitory effect of antisense oligonucleotides on gene expression were used to determine the roles of various parts of the leader. It was found that the 5'- and 3'-ends of the leader are absolutely required for translation whereas the middle part is apparently dispensable. These results confirm the data already reported from transient expression experiments with protoplasts. However, the in vitro data suggest in contrast to protoplast experiments that only two relatively short regions at both ends, approximately 100 nt each, are required. The in vitro system provides tools for further studying the shunt model at the molecular level and for examining the involvement of proteins in this mechanism. Shunting was also found to occur with the rice tungro bacilliform virus leader. As wheat is neither a host plant of cauliflower mosaic virus nor rice tungro bacilliform virus, the shunt seems to be host independent, a finding that deviates from earlier studies in protoplasts.

Badnavirus↗

Assessing public health performance in Iowa's counties.

Local health agencies in Iowa were surveyed to assess the performance of public health practices in their communities. Responses were received from 97 percent of counties. Less than 50 percent of counties were performing half of the indicators of the Assessment function. Policy Development functions also were frequently not performed. Performance was best in the Assurance function, with 86 percent of counties reporting that they inform and educate the public. However, the other three types of Assurance practices (Manage, Implement, and Evaluate) were performed less frequently. Comparison of the performance of Iowa's rural counties reveals a profile nearly identical to that reported elsewhere for a group of six other states.

Benchmarking↗

Progressive cardiomyopathic lentiginosis: report of six cases and one autopsy.

Progressive cardiomyopathic lentiginosis (PCL) is a syndrome with progressive multisystem abnormalities. Lentigines, the cutaneous hallmark, are usually present from early age and are of utmost diagnostic value. Six children with PCL are reported. The most constant diagnostic features in this age group were multiple cutaneous lentigines, structural cardiac anomalies, and electrocardiographic alterations. Less constant findings were neurosensory deafness, short stature, and osseous, ocular, and genitourinary abnormalities.

Arrhythmias, Cardiac↗

Ring chromosome 6 in a child with minimal abnormalities.

We describe a boy with a ring chromosome 6 and short stature, mild micrognathia, and bilateral transitional/simian creases. Five other patients with a ring 6 have been reported. The clinical and cytogenetic observations of all six patients are compared and discussed.

Body Height↗

Merging PICU and MICU: expanding nurse competencies.

Unit mergers offer an opportunity for nurses to acquire additional skills. A model for unit mergers is presented. The authors describe how didactic and clinical competencies serve as a foundation upon which the nurse develops proficiency and expertise in a new subspecialty.

Adult↗