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At least 523 records · Page 29Linked to original sources

PubMed2003

Topiramate protects against glutamate- and kainate-induced neurotoxicity in primary neuronal-astroglial cultures.

Potential neuroprotective effects of the antiepileptic drug (AED) topiramate (TPM) were evaluated using primary neuronal-astroglial cultures or astroglial-enriched cultures from newborn rats exposed to excitotoxic concentrations of glutamate (Glu) or kainate. Neurons expressed functional Glu receptors of the NMDA and AMPA/kainate types as evaluated by immunocytochemistry and Ca(2+) imaging. When Glu (10 mM) was added to 9-10-day cultures incubated with the fluorescent dye calcein/AM for 5h, there was a marked cell loss in both culture types, but was more pronounced in the neuronal-astroglial cultures. When TPM (5-10 microM) was included in the medium together with Glu, the amount of surviving cells was significantly higher in the neuronal-astroglial cultures, but not in the astroglial-enriched cultures. Immuno-labeling of the cultures revealed an enhanced survival of MAP positive neuronal cells when TPM was included in the Glu containing medium. As TPM has a proven negative modulatory effect on kainate activated receptors, neuronal-astroglial cultures were further exposed to excitotoxic concentrations of kainate (100 microM) and analyzed immunohistochemically. Significantly more MAP positive neurons survived in the TPM containing medium and showed a morphology similar to untreated cells. Valproate and phenytoin were used as reference AEDs. In conclusion, our results demonstrate a protective effect of TPM upon neuronal cells in primary culture, exposed to excitotoxic levels of Glu or kainate.

Animals↗

PubMed1991

Characterization of the tryptic map of recombinant DNA derived tissue plasminogen activator by high-performance liquid chromatography-electrospray ionization mass spectrometry.

A detailed tryptic map is presented for recombinant human tissue plasminogen activator (rt-PA). Electrospray ionization mass spectrometry is utilized as an on-line HPLC detector for tryptic mapping of this glycoprotein. The additional dimension provided by mass spectrometry gives considerably more detail about the complex tryptic map and significantly enhances the high-resolution chromatographic separation by distinguishing by mass any coeluting components. Through this improvement, the proline isomers of a tryptic peptide were observed eluting over a broad range of retention times. The glycopeptides of rt-PA are observed as well as any corresponding nonglycosylated peptides. In addition, the carbohydrate heterogeneity is readily observed, allowing analysis of the carbohydrate composition. The characteristic diagonal patterns formed by glycopeptides in a contour plot of the data allow rapid recognition of the glycopeptides.

Amino Acid Sequence↗

PubMed1996

Substrate specificity of IphP, a cyanobacterial dual-specificity protein phosphatase with MAP kinase phosphatase activity.

The substrate specificity of the cyanobacterial dual-specificity protein phosphatase, IphP, was explored using a variety of potential substrates. The enzyme displayed phosphomonoesterase activity toward a broad range of peptide, protein, and low molecular weight organophosphate compounds. It displayed little or no hydrolase activity toward phosphodiesters, phosphoramides, carboxyl esters, or sulfoesters. However, it did display measurable pyrophosphatase activity, especially toward ADP and ATP. Among the low molecular weight phosphomonoesters, the presence of an aromatic ring either as part of the leaving group alcohol or immediately adjacent thereto, as in 5'-AMP, was a strong positive determinant for hydrolysis. Among peptide and protein substrates, a rough, but imperfect, correlation between charge character and hydrolysis was noted in which proteins and phosphorylation sites of an acidic nature seemed favored. Heparin affected IphP activity in a substrate-dependent manner. Toward small organophosphates, heparin had no significant effect, but it was inhibitory toward most protein and peptide substrates. However, toward phosphoseryl casein and MAP kinase, it enhanced activity as much as 10-fold. This enhancement was attributed to the ability of heparin to bind to these substrate proteins, as well as IphP, and recruit them to the same microenvironment.

Adenosine Diphosphate↗

PubMed2004

Tissue perfusion essential for spermatogenesis and outcome of testicular sperm extraction (TESE) for assisted reproduction.

PURPOSE: In order to determine if there are areas of major and minor perfusion in a single testicle and if the quality of sperm is correlated with quantity of perfusion we collected testicle tissue for TESE in accordance to the local testicle tissue perfusion. METHODS: A patient undergoing TESE underwent testicular perfusion mapping using contrast enhanced ultrasound. The exposed tissue was scanned with a Laser Doppler scanner and perfusion rates were determined measuring tissue perfusion units (TPUs). Tissue was biopsied and sperm were selected and prepared for assisted reproduction. RESULTS: The total amount of isolated sperm correlated highly with the intensity of tissue perfusion showing high number of sperm in areas with high TPUs. CONCLUSIONS: This is the first demonstration that sperm quality and quantity is depending on tissue perfusion within the testicle. To further improve infertility treatment we propose that random biopsies could be replaced by perfusion-dependent collection of testicular tissue.

Biopsy↗

PubMed2005

Regulated cell-to-cell variation in a cell-fate decision system.

Here we studied the quantitative behaviour and cell-to-cell variability of a prototypical eukaryotic cell-fate decision system, the mating pheromone response pathway in yeast. We dissected and measured sources of variation in system output, analysing thousands of individual, genetically identical cells. Only a small proportion of total cell-to-cell variation is caused by random fluctuations in gene transcription and translation during the response ('expression noise'). Instead, variation is dominated by differences in the capacity of individual cells to transmit signals through the pathway ('pathway capacity') and to express proteins from genes ('expression capacity'). Cells with high expression capacity express proteins at a higher rate and increase in volume more rapidly. Our results identify two mechanisms that regulate cell-to-cell variation in pathway capacity. First, the MAP kinase Fus3 suppresses variation at high pheromone levels, while the MAP kinase Kss1 enhances variation at low pheromone levels. Second, pathway capacity and expression capacity are negatively correlated, suggesting a compensatory mechanism that allows cells to respond more precisely to pheromone in the presence of a large variation in expression capacity.

CDC28 Protein Kinase, S cerevisiae↗

PubMed2001

Physical localization and order of genes in the class I region of the bovine MHC.

Fluorescence in situ hybridization (FISH) analyses were used to order 16 bacterial artificial chromosomes (BAC) clones containing loci from the bovine lymphocyte antigen (BoLA) class I and III regions of bovine chromosome 23 (BTA23). Fourteen of these BACs were assigned to chromosomal band locations of mitotic and pachytene chromosomes by single- and dual-colour FISH. Dual-colour FISH confirmed that class II DYA is proximal to and separated from BoLA class I genes by approximately three chromosome bands. The FISH results showed that tumour necrosis factor alpha (TNFA), heat shock protein 70 (HSP70.1) and 21 steroid dehydrogenase (CYP21) are closely linked in the region of BTA23 band 22 along with BoLA class I genes, and that male enhanced antigen (MEA) mapped between DYA and the CYP21/TNFA/HSP70.1 gene region. All BAC clones containing BoLA class I genes mapped distal to CYP21/TNFA/HSP70.1 and centromeric to prolactin (PRL). Myelin oligodendrocyte glycoprotein (MOG) was shown to be imbedded within the BoLA class I gene cluster. The cytogenetic data confirmed that the disrupted distribution of BoLA genes is most likely the result of a single large chromosomal inversion. Similar FISH results were obtained when BoLA DYA and class I BAC clones were mapped to discrete chromosomal locations on the BTA homologue in white-tailed deer, suggesting that this chromosomal inversion predates divergence of the advanced ruminant families from a common ancestor.

Animals↗

PubMed2002

Governor of the glnAp2 promoter of Escherichia coli.

Low-affinity sites for the activator NRI-P (NtrC-P) that map between the enhancer and the glnAp2 promoter were responsible for limiting promoter activity at high concentrations of NRI approximately P in intact cells and in an in vitro transcription system consisting of purified bacterial components. That is, the low-affinity sites constitute a 'governor', limiting the maximum promoter activity. As the governor sites are themselves far from the promoter, they apparently act either by preventing the formation of the activation DNA loop that brings the enhancer-bound activator and the promoter-bound polymerase into proximity or by preventing a productive interaction between the enhancer-bound activator and polymerase. The combination of potent enhancer and governor sites at the glnAp2 promoter provides for efficient activation of the promoter when the activator concentration is low, while limiting the maximum level of promoter activity when the activator concentration is high.

Bacterial Proteins↗

PubMed1987

Relief of nonhemispheric symptoms in low flow states by anterior circulation revascularization: a physiologic approach.

Operative intervention remains controversial for patients with transient nonhemispheric symptoms with occlusive disease of both the anterior and posterior cerebral circulations. In addition to the standard evaluation of these patients, we have used stable xenon-enhanced computed tomographic mapping of cerebral blood flow (Xe/CT CBF). This relatively new and potentially widely available CBF methodology, by measuring approximately 30,000 CBF values within each of three CT levels, provides a readily interpretable means of evaluating extremes of hemodynamic compromise within any or all vascular territories. In the past 30 months, Xe/CT CBF studies in 300 patients with occlusive vascular disease have identified nine patients with global low flow and nonhemispheric symptoms (vertigo, lightheadedness, and/or blurred vision). Blood pressures determined by ocular pneumoplethysmography of Gee were markedly abnormal with reduced ocular/brachial ratios. Each patient had a combination of both segmental carotid and vertebrobasilar occlusive disease. Each patient had a flow-augmenting procedure performed on the anterior circulation in an attempt to improve global flow: carotid endarterectomy (two patients), subclavian-external carotid bypass (one patient), and superficial temporal artery-middle cerebral artery bypass (six patients). In each case disabling transient symptoms were relieved. There were no operative deaths, but one stroke occurred, probably as a result of a brief period of postoperative hypotension. Postoperative Xe/CT CBF studies show a long-term improved global CBF in all patients.

Brain↗

PubMed2000

An asn to lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling.

alpha(2A)-Adrenergic receptors (alpha(2A)AR) are presynaptic autoinhibitory receptors of noradrenergic neurons in the central and peripheral sympathetic nervous systems, which act to dynamically regulate neurotransmitter release. Signaling through the G(i)/G(o) family of G-proteins, the receptor subserves numerous homeostatic and central nervous system functions. A single nucleotide polymorphism of this receptor, which results in an Asn to Lys substitution at amino acid 251 of the third intracellular loop, was identified in the human population. The frequency of Lys-251 was 10-fold greater in African-Americans than in Caucasians, but was not associated with essential hypertension. To determine the consequences of this substitution, wild-type and Lys-251 receptors were expressed in CHO and COS-7 cells. Expression, ligand binding, and basal receptor function were unaffected by the substitution. However, agonist-promoted [(35)S]GTPgammaS binding was approximately 40% greater with the Lys-251 receptor. This enhanced agonist function was observed with catecholamines, azepines, and imidazolines albeit to different degrees. In studies of agonist-promoted functional coupling to G(i), the polymorphic receptor displayed enhanced inhibition of adenylyl cyclase (60 +/- 4. 4 versus 46 +/- 4.1% inhibition) and markedly enhanced stimulation of MAP kinase (57 +/- 9 versus 15- +/- 2-fold increase over basal) compared with wild-type alpha(2A)AR. The potency of epinephrine in stimulating inositol phosphate accumulation was increased approximately 4 fold with the Lys-251 receptor. Unlike previously described variants of G-protein-coupled receptors, where the minor species causes either a loss of function or increased non-agonist function, Lys-251 alpha(2A)AR represents a new class of polymorphism whose phenotype is a gain of agonist-promoted function.

Adenylyl Cyclase Inhibitors↗

PubMed1989

Dual cis-acting negative regulatory elements located upstream of the mouse DNA polymerase beta gene.

A 2,200 base pair (bp) fragment containing the 5'-flanking region of the mouse DNA polymerase beta gene was placed adjacent to and upstream of the chloramphenicol acetyl transferase (CAT)-coding region of the CAT vector. A transient expression assay of CAT activity in mouse NIH/3T3 cells transfected with this recombinant plasmid or a set of its 5'-deletion derivatives was carried out to identify a cis-acting regulatory element(s) for DNA polymerase beta gene expression. Depending on the extent of the deletion, CAT activity was dramatically increased, indicating the existence of a negative regulatory region which could be divided into two distinct domains: removal of the first domain (NRE-I), nucleotides -1860 to -1580 (+1 denotes the position of 5'-most proximal transcription initiation site), caused two to three-fold stimulation of CAT activity, and removal of the second domain (NRE-II), nucleotides -828 to -456, stimulated CAT expression another two to three-fold. When an 1,864-bp segment containing these negative regulatory elements (-2190 to -327) was inserted in the plasmid carrying the simian virus 40 early promoter and enhancer-directed CAT gene, it inhibited the CAT expression relatively independently of the orientation of insertion and the distance from the promoter-enhancer. We also mapped the promoter element of the DNA polymerase beta gene to within a 133-bp DNA fragment from nucleotide position -100 to +33. Either the NRE-I region or the NRE-II region alone can inhibit DNA polymerase beta gene promoter function.

Animals↗

PubMed1997

TAFII250-dependent transcription of cyclin A is directed by ATF activator proteins.

A specific mutation in TAFII250, the largest subunit of the transcription factor TFIID, disrupts cell growth control in the temperature-sensitive mutant hamster cell line ts13. Transcription from the cyclin A and D1 but not the c-fos and myc promoters is also dramatically reduced in ts13 cells at the nonpermissive temperature. These findings provide an intriguing link between TAF-mediated transcriptional regulation and cell cycle progression. Here we report the mapping of an enhancer element in the cyclin A promoter (TSRE) that responds to mutations in TAFII250. An analysis of chimeric promoter constructs reveals that the cyclin A TSRE can confer TAFII250 dependence to the core promoter of c-fos. In addition, reciprocal hybrid promoter constructs suggest that TAFII250 also contributes to the transcriptional properties of the cyclin A core promoter. We have purified and identified cellular activators that specifically bind to the TSRE and mediate transcription in a TAFII250-dependent manner. By micropeptide sequencing, we determined that TSRE-binding proteins include members of the activating transcription factor (ATF) family. These results suggest that the ts13 mutation of TAFII250 has compromised the ability of TFIID to mediate activation of transcription by specific enhancer factors such as ATF, as well as to perform certain core promoter functions. These defects in TAFII250 apparently result in the down-regulation of key molecules, such as cyclin A, which may be responsible for the ts13 cell cycle arrest phenotype.

Animals↗

PubMed1998

Endocardial and epicardial ablation guided by nonsurgical transthoracic epicardial mapping to treat recurrent ventricular tachycardia.

INTRODUCTION: An epicardial site of origin of ventricular tachycardia (VT) may explain unsuccessful endocardial radiofrequency (RF) catheter ablation. A new technique to map the epicardial surface of the heart through pericardial puncture was presented recently and opened the possibility of using epicardial mapping to guide endocardial ablation or epicardial catheter ablation. We report the efficacy and safety of these two approaches to treat 10 consecutive patients with VT and Chagas' disease. METHODS AND RESULTS: Epicardial mapping was carried out with a regular steerable catheter introduced into the pericardial space. An epicardial circuit was found in 14 of 18 mapable VTs induced in 10 patients. Epicardial mapping was used to guide endocardial ablation in 4 patients and epicardial ablation in 6. The epicardial earliest activation site occurred 107+/-60 msec earlier than the onset of the QRS complex. At the epicardial site used to guide endocardial ablation, earliest activation occurred 75+/-55 msec before the QRS complex. Epicardial mid-diastolic potentials and/or continuous electrical activity were seen in 7 patients. After 4.8+/-2.9 seconds of epicardial RF applications, VT was rendered noninducible. Hemopericardium requiring drainage occurred in 1 patient; 3 others developed pericardial friction without hemopericardium. Patients remain asymptomatic 5 to 9 months after the procedure. Interruption during endocardial pulses occurred after 20.2+/-14 seconds (P = 0.004), but VT was always reinducible and the patients experienced a poor outcome. CONCLUSION: Epicardial mapping does not enhance the effectiveness of endocardial pulses of RF. Epicardial applications of RF energy can safely and effectively treat patients with VT and Chagas' disease.

Adult↗

PubMed2001

Protein kinase C-delta regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase.

The procoagulant thrombin promotes the adhesion of polymorphonuclear leukocytes to endothelial cells by a mechanism involving expression of intercellular adhesion molecule 1 (ICAM-1) via an NF-kappaB-dependent pathway. We now provide evidence that protein kinase C-delta (PKC-delta) and the p38 mitogen-activated protein (MAP) kinase pathway play a critical role in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. We observed the phosphorylation of PKC-delta and p38 MAP kinase within 1 min after thrombin challenge of human umbilical vein endothelial cells. Pretreatment of these cells with the PKC-delta inhibitor rottlerin prevented the thrombin-induced phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals downstream of PKC-delta. Inhibition of PKC-delta or p38 MAP kinase by pharmacological and genetic approaches markedly decreased the thrombin-induced NF-kappaB activity and resultant ICAM-1 expression. The effects of PKC-delta inhibition were secondary to inhibition of IKKbeta activation and of subsequent NF-kappaB binding to the ICAM-1 promoter. The effects of p38 MAP kinase inhibition occurred downstream of IkappaBalpha degradation without affecting the DNA binding function of nuclear NF-kappaB. Thus, PKC-delta signals thrombin-induced ICAM-1 gene transcription by a dual mechanism involving activation of IKKbeta, which mediates NF-kappaB binding to the ICAM-1 promoter, and p38 MAP kinase, which enhances transactivation potential of the bound NF-kappaB p65 (RelA).

Cells, Cultured↗

PubMed2002

ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents.

We examined whether ATP stimulation of P2X purinoceptors would raise blood pressure in decerebrate cats. Femoral arterial injection of the P2X receptor agonist alpha,beta-methylene ATP into the blood supply of the triceps surae muscle induced a dose-dependent increase in arterial blood pressure. The maximal increase in mean arterial pressure (MAP) evoked by 0.1, 0.2, and 0.5 mM alpha,beta-methylene ATP (0.5 ml/min injection rate) was 6.2 +/- 2.5, 22.5 +/- 4.4, and 35.2 +/- 3.9 mmHg, respectively. The P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (2 mM ia) attenuated the increase in MAP elicited by intra-arterial alpha,beta-methylene ATP (0.5 mM), whereas the P2Y receptor antagonist reactive blue 2 (2 mM ia) did not affect the MAP response to alpha,beta-methylene ATP. In a second group of experiments, we tested the hypothesis that ATP acting through P2X receptors would sensitize muscle afferents and, thereby, augment the blood pressure response to muscle stretch. Two kilograms of muscle stretch evoked a 26.5 +/- 4.3 mmHg increase in MAP. This MAP response was enhanced when 2 mM ATP or 0.1 mM alpha,beta-methylene ATP (0.5 ml/min) was arterially infused 10 min before muscle stretch. Furthermore, this effect of ATP on the pressor response to stretch was attenuated by 2 mM pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (P < 0.05) but not by the P1 purinoceptor antagonist 8-(p-sulfophenyl)-theophylline (2 mM). These data indicate that activation of ATP-sensitive P2X receptors evokes a skeletal muscle afferent-mediated pressor response and that ATP at relatively low doses enhances the muscle pressor response to stretch via engagement of P2X receptors.

Adenosine Triphosphate↗

PubMed2004

Endogenous endothelin attenuates the pressor response to acute environmental stress via the ETA receptor.

Clinical studies have documented an abrupt rise in plasma endothelin-1 (ET-1) coincident with an increase in mean arterial pressure (MAP) during the response to acute stress. We therefore examined the ET(A) and ET(B) receptor-dependent effects of ET-1 on the pressor response to acute environmental stress in ET-1-dependent hypertension. Stress was induced by administration of air jet pulses (3 min) in ET(B) receptor-deficient (ET(B) sl/sl) rats fed normal salt (NS; 0.8% NaCl), high salt (HS; 8% NaCl), and HS plus the ET(A) receptor antagonist ABT-627 (5 mg.kg(-1).day(-1)) on successive weeks. MAP was chronically monitored by telemetry. Total pressor response (area under the curve) was significantly reduced in ET(B) sl/sl rats maintained on a HS vs. NS diet [-6.8 mmHg (SD 18.7) vs. 29.3 mmHg (SD 8.1) x 3 min, P < 0.05]. Conversely, the total pressor response was augmented in both wild-type [34.2 mmHg (SD 29.2) x 3 min, P < 0.05 vs. NS] and ET(B) sl/sl rats [49.1 mmHg (SD 11.8) x 3 min, P < 0.05 vs. NS] by ABT-627. Blockade of ET(B) receptors in Sprague-Dawley rats caused an increase in basal MAP that was enhanced by HS and lowered by mixed ET(A)/ET(B) receptor antagonism; none of these treatments, however, had any effect on the pressor response. These data demonstrate that increasing endogenous ET-1 suppresses the pressor response to acute stress through ET(A) receptor activation in a genetic model of ET-1-dependent hypertension. These results are consistent with reports that ET-1 can attenuate sympathetically mediated responses.

Acute Disease↗

PubMed2002

Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism: an MRI investigation in rat brain.

BACKGROUND AND PURPOSE: Thrombolytic treatment of stroke carries the risk of hemorrhagic transformation. Therefore, the potential of MRI for prediction of recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to identify patients in whom rtPA treatment may provoke such complications. METHODS: Spontaneously hypertensive rats (SHR) (n=9) were submitted to middle cerebral artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of 10 mg/kg rtPA. Untreated SHR (n=9) were infused with saline. MRI imaging was performed before treatment and included apparent diffusion coefficient (ADC), T2, and perfusion mapping and contrast enhancement with gadolinium-DTPA. The distribution of intracerebral hemorrhages was studied 3 days later by histological staining. RESULTS: Clot embolism led to the rapid decline of ADC in the territory of the occluded artery. Tissue lesion volume derived from ADC imaging increased by 155+/-69% in the untreated animals and by 168+/-87% in the treated animals (P=NS), determined on the histological sections after 3 days. This same lesion growth in both groups indicated absence of therapeutic effect after 3-hour treatment delay. Hemorrhagic transformations were significantly more frequent in treated SHR (P<0.05). In untreated rats, hemorrhages were found in the border zone of the ischemic territory; in treated animals, hemorrhagic transformations occurred in the ischemic core region. rtPA-induced hemorrhages were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or perfusion imaging. The region of contrast enhancement colocalized with subsequent bleeding in these animals. CONCLUSIONS: The disturbance of blood-brain barrier but not of other MR parameters allows risk assessment for hemorrhagic transformation induced by subsequent thrombolytic treatment.

Animals↗

PubMed2004

Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

Animals↗

PubMed2004

Coupling computer-interpretable guidelines with a drug-database through a web-based system--The PRESGUID project.

BACKGROUND: Clinical Practice Guidelines (CPGs) available today are not extensively used due to lack of proper integration into clinical settings, knowledge-related information resources, and lack of decision support at the point of care in a particular clinical context. OBJECTIVE: The PRESGUID project (PREScription and GUIDelines) aims to improve the assistance provided by guidelines. The project proposes an online service enabling physicians to consult computerized CPGs linked to drug databases for easier integration into the healthcare process. METHODS: Computable CPGs are structured as decision trees and coded in XML format. Recommendations related to drug classes are tagged with ATC codes. We use a mapping module to enhance computerized guidelines coupling with a drug database, which contains detailed information about each usable specific medication. In this way, therapeutic recommendations are backed up with current and up-to-date information from the database. RESULTS: Two authoritative CPGs, originally diffused as static textual documents, have been implemented to validate the computerization process and to illustrate the usefulness of the resulting automated CPGs and their coupling with a drug database. We discuss the advantages of this approach for practitioners and the implications for both guideline developers and drug database providers. Other CPGs will be implemented and evaluated in real conditions by clinicians working in different health institutions.

Computer Graphics↗