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Biomedical subjects

A Vidal

Publications and source records attributed to A Vidal.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of imidazo[1,2-a]pyrimidine derivatives on leukocyte function.

OBJECTIVE AND DESIGN: A series of six imidazo[1,2-a]pyrimidine (IP) derivatives were evaluated for their effects on leukocyte functions in vitro as well as on the inflammatory response induced by zymosan in the mouse air pouch. MATERIALS AND SUBJECTS: Human neutrophils and murine peritoneal macrophages were used for in vitro assays. Mouse air pouch was performed in Swiss mice. TREATMENT: Test compounds were incubated with either human neutrophils or mouse peritoneal macrophages at concentrations not showing cytotoxic effects. For in vivo experiments, IPs were injected into the air pouch. METHODS: Elastase and myeloperoxidase release, superoxide generation and LTB4 production were assayed in human neutrophils treated with different stimuli. Mouse peritoneal macrophages were stimulated with lipopolysaccharide (LPS), followed by determination of nitrite and PGE2 levels in supernatants. Zymosan was injected into six days-old mouse air pouches. Dunnett's t-test was employed for statistical analysis. RESULTS: All IPs inhibited human neutrophil degranulation with IC50 values in the microM range. IP-1, IP-2 and IP-5 also decreased superoxide generation. In LPS-stimulated macrophages, IP-4 and IP-6 inhibited nitrite production with a moderate reduction in PGE2 generation. In addition, these two compounds at 100 nmol/pouch inhibited leukocyte migration and LTB4 levels in the exudate of the mouse air pouch. CONCLUSIONS: Imidazo[1,2-a]pyrimidines are a class of compounds with antiinflammatory potential.

Animals↗
PubMed2001

The energetics of binding of a signal peptide to lipid bilayers: the role of bilayer properties.

The interactions between a signal peptide and a variety of lipid bilayers have been studied with direct binding assays, CD and isothermal titration calorimetry. We find that the binding of this peptide is influenced by charges and dipoles located in the bilayer interfacial region, as well as by the presence of cholesterol in the bilayer. These studies show that bilayer compositional and mechanical variations found in different biological membranes can affect the partitioning of peptides into the bilayer.

Amino Acid Sequence↗
PubMed2001

Effect of some hexahydroimidazo[1,2-c]pyrimidines in inflammatory responses involving leucocytes and macrophages.

We have studied the effects of some hexahydroimidazo[1,2-c]pyrimidine derivatives (HIPs) on leucocyte functions in-vitro and we have assayed the anti-inflammatory activity of these compounds in two models of inflammation. All HIPs inhibited the human neutrophil degranulation process and superoxide generation at concentrations in the microM range. In mouse peritoneal macrophages stimulated with lipopolysaccharide, HIP-4 and HIP-5 inhibited nitrite production without affecting prostaglandin E2 (PGE2) accumulation. HIP-4 was also active in the zymosan-injected mouse air pouch model (at 100 nmol/pouch), with significant reductions in leucocyte migration and PGE2 and leukotriene B4 levels in the air pouch exudate. To confirm the anti-inflammatory effects of this compound, we tested HIP-4 orally (10-40 mg kg(-1)) on carrageenan mouse-paw oedema where it exerted a dose-dependent inhibition of paw swelling with significant reductions of myeloperoxidase and elastase activity and PGE2 levels in paw homogenates. This study demonstrates that some HIPs inhibit leucocyte functions and one of these derivatives (HIP-4) shows anti-inflammatory activity when administered by the oral route, which can be related to inhibition of leucocyte migration.

Animals↗
PubMed2000

New stereoselective intramolecular

Efficient 1,4-asymmetric induction has been achieved in the highly stereocontrolled intramolecular [2 + 2] cycloadditions between ketenimines and imines, leading to 1,2-dihydroazeto[2, 1-b]quinazolines. The chiral methine carbon adjacent to the iminic nitrogen controls the exclusive formation of the cycloadducts with relative trans configuration at C2 and C8. The stepwise mechanistic model, based on theoretical calculations, fully supports the stereochemical outcome of these cycloadditions.

Journal Article↗
PubMed2000

Highly efficient induction of chirality in intramolecular

Highly stereocontrolled, intramolecular [2 + 2] cycloadditions between ketenimines and imines leading to 1,2-dihydroazeto[2, 1-b]quinazolines have been achieved. The source of stereocontrol is a chiral carbon atom adjacent either to the iminic carbon or nitrogen atom. In the first case, the stereocontrol stems from the preference for the axial conformer in the first transition structure. In the second case, the origin of the stereocontrol lies on the two-electron stabilizing interaction between the C-C bond being formed and the sigma orbital corresponding to the polar C-X bond, X being an electronegative atom. These models can be extended to other related systems for predicting the stereochemical outcome in this intramolecular reaction.

Journal Article↗
PubMed2000

Cell-cycle inhibitors: three families united by a common cause.

In the cellular program leading to DNA synthesis, signals that drive cells into S-phase converge at the level of CDK activity. The products of at least three different gene families, Ink4, Cip/Kip and the pRb pocket-protein family, suppress S-phase entry. Ink4 proteins act by antagonizing the formation and activation of cyclin D-CDK4 complexes, of which the ultimate downstream target as related to S-phase entry appears to be pRb. Cip/Kip inhibitors impinge upon that pathway by inhibiting CDK2 kinases that participate in the inactivation of pRb and, like cyclin E, may also have roles independent of pRb. How the activities of these three classes of proteins are coordinated remains obscure. In recent years, development of mouse models has accelerated the elucidation of this complex network, showing roles that are sometimes cooperative and sometimes overlapping. We will discuss the interrelationships between Cip/Kip inhibitors and the components of the pRb pathway, and how their activities ultimately regulate cell proliferation.

Animals↗
PubMed2000

Conversion of N-acyl-4-acyloxy-beta-lactams into 1,3-oxazin-6-ones: two consecutive pseudopericyclic processes

N-Acyl-4-acyloxy-beta-lactams are converted into 1,3-oxazin-6-ones under basic conditions. This transformation is believed to proceed via N-acylazetones, which rearrange to the final products by a sequence of two electrocyclic processes. The calculated (RHF and B3LYP) transition structures of both concerted reactions are shown to present characteristic pseudopericyclic orbital topologies.

Journal Article↗
PubMed2000

[Evaluation and validation of Omron Hem 705 CP and Hem 706/711 monitors for self-measurement of blood pressure].

OBJECTIVE: To validate two devices for self-measurement of blood pressure--The Omron Hem-705CP and the Omron Hem 706/711--according to the revised protocol of the British Hypertension Society (BHS). The results were also analysed according to the criteria for accuracy of the revised standard of the Association for the Advancement of Medical Instrumentation (AAMI). DESIGN: The British Hypertension protocol for the evaluation of blood pressure measuring devices. SETTING: Primare care. Zone III Health Care in Albacete (Spain). PARTICIPANTS: 95 subjects to validate the Omron 706/711 and 100 subjets to Omron 705. RESULTS: Two monitors surpassed the validation according to the standars set out by the BHS protocol (705 with a A grading for SBP and DBP, 706/711 obtained a B grading for SBP and an A grading for DBP and a PASS for SBP and DBP. Upon analyzing the behavior of the appliances by subgroups of BP measures (high, mid, and low), 705 for SBP > 160 mmHg obtained a B grading for the BHS protocol, but it did not pass the accuracy AAMI criteria (SD, 8.5, but difference between observers-device is -0.1 mmHg). The rest of subgroups of BP obtained a A grading for the BHS protocol and a PASS (AAMI). 706/711 surpassed in all BP subgroups BHS protocol, for DBP 80-100, SBP > 160 and DBP > 100 with a B grading, for the rest of BP subgroups obtained a B grading and a PASS (AAMI). CONCLUSIONS: On the basis of these results, we conclude both monitors Omron HEM 706/711 and the Omron 705CP surpassed the accuracy criteria required for BHS and AAMI, and can be recommended for clinical use.

Adolescent↗
PubMed2000

Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis.

The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and COX-2 endotoxin induction in mouse peritoneal macrophages has been studied. Three of these compounds inhibited nitrite and PGE2 accumulation in a concentration dependent-manner at microM range. None of these active compounds affected iNOS, COX-2, COX-1 or PLA2 activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil inflammatory responses (LTB4 biosynthesis and superoxide or elastase release). Active compounds were assayed by oral administration in the mouse air pouch model, where they inhibited nitrite accumulation without affecting PGE2 levels or leukocyte migration.

Animals↗
PubMed2000

Angiotensin-converting enzyme (ACE) gene polymorphisms, serum ACE activity and blood pressure in a Spanish-Mediterranean population.

Angiotensin-converting enzyme (ACE) levels and ACE gene polymorphisms have been related with hypertension but with contradictory results between populations. We have investigated the association among the allelic distribution of the insertion-deletion (I/D) polymorphism of the ACE gene, identified by polymerase chain reaction (PCR), serum ACE activity determined by spectrophotometry, and the blood pressure (BP), in a Mediterranean population in the southwest of Europe. A total of 1322 randomised individuals were analysed, and a comparative study was conducted analysing 205 individuals from the group with highest BP (fifth quintyl) and 196 from the group with lowest BP (first quintyl). In addition we have studied the frequencies of alleles in separated groups of women and men. We conclude that in this population there is no association between I/D polymorphism and hypertension. However, we have found a statistically significant association between the presence of the D allele in the genotypes and an elevation of serum ACE activity.

Blood Pressure↗
PubMed2000

LEFPS1, a tomato farnesyl pyrophosphate gene highly expressed during early fruit development.

Farnesyl pyrophosphate synthase (FPS) catalyzes the synthesis of farnesyl pyrophosphate, a key intermediate in sterol and sesquiterpene biosynthesis. Using a polymerase chain reaction-based approach, we have characterized LeFPS1, a tomato (Lycoperscion esculentum cv Wva 106) fruit cDNA, which encodes a functional FPS. We demonstrate that tomato FPSs are encoded by a small multigenic family with genes located on chromosomes 10 and 12. Consistent with farnesyl pyrophosphate requirement in sterol biosynthesis, FPS genes are ubiquitously expressed in tomato plants. Using an LeFPS1 specific probe, we show that the corresponding gene can account for most of FPS mRNA in most plant organs, but not during young seedling development, indicating a differential regulation of FPS genes in tomato. FPS gene expression is also under strict developmental control: FPS mRNA was mainly abundant in young organs and decreased as organs matured with the exception of fruits that presented a biphasic accumulation pattern. In this latter case in situ hybridization studies have shown that FPS mRNA is similarly abundant in all tissues of young fruit. Taken together our results suggest that several FPS isoforms are involved in tomato farnesyl pyrophosphate metabolism and that FPS genes are mostly expressed in relation to cell division and enlargement.

Alkyl and Aryl Transferases↗
PubMed2000

A U-rich element in the 5' untranslated region is necessary for the translation of p27 mRNA.

Increased translation of p27 mRNA correlates with withdrawal of cells from the cell cycle. This raised the possibility that antimitogenic signals might mediate their effects on p27 expression by altering complexes that formed on p27 mRNA, regulating its translation. In this report, we identify a U-rich sequence in the 5' untranslated region (5'UTR) of p27 mRNA that is necessary for efficient translation in proliferating and nonproliferating cells. We show that a number of factors bind to the 5'UTR in vitro in a manner dependent on the U-rich element, and their availability in the cytosol is controlled in a growth- and cell cycle-dependent fashion. One of these factors is HuR, a protein previously implicated in mRNA stability, transport, and translation. Another is hnRNP C1 and C2, proteins implicated in mRNA processing and the translation of a specific subset of mRNAs expressed in differentiated cells. In lovastatin-treated MDA468 cells, the mobility of the associated hnRNP C1 and C2 proteins changed, and this correlated with increased p27 expression. Together, these data suggest that the U-rich dependent RNP complex on the 5'UTR may regulate the translation of p27 mRNA and may be a target of antimitogenic signals.

5' Untranslated Regions↗
PubMed2000

Parallel segmentation and rendering using clusters of PCs.

Clinics have to deal currently with hundreds of 3D images a day. 3D Medical Images contain a huge amount of data, and thus, very expensive and powerful systems are required in order to process them. The present work shows the features of a software parallel computing package developed at the Universidad Politécnica de Valencia, under the European Project HIPERCIR. http:¿hiperttn.upv.es/hipercir. Project HIPERCIR is aimed at reducing the time and requirements for processing and visualising 3D images with low-cost solutions, such as networks of PCs running standard operating systems (Windows 95/98/NT). This project is being developed by a consortium formed by medical image processing and parallel computing experts from the Universidad Politécnica de Valencia (UPV), experts on biomedical software and radiology clinic experts.

Computer Systems↗
PubMed2000

[Comparative proximal and mineral analysis of iguana,poultry and beef meats].

Raw meat samples from iguana, poultry and beef cattle specimens were used to compare proximal (g/100 g) and mineral (mg/100 g) composition. Iguana meat was obtained by dissecting whole specimens (Iguana iguana) captured at a ranch (n = 20). Thighs and breasts were separated from broiler (either chilled or frozen) carcasses (n = 20), and deboned to represent chicken meat samples, whereas 2.5-cm-thick longissimus (ribeyes) steaks were removed from carcasses and frozen to represent beef of several breed types (n = 20). The one-way analysis of variance performed by the least squares method (LS Means) showed specie affected significantly (p > 0.05) all composition variables under study. Moisture content did not differ between iguana and chicken meats (74.7 y 74.9%, respectively) whereas beef samples had the lowest water content (73%) (p < 0.01). LS means for protein content showed beef samples (22.3%) were highest (p < 0.05) in this nutrient, iguana meat being intermediate (20.8%). Chicken meat presented the highest amount of total lipids (7.75 +/- 0.20 g/100 g) (p < 0.01) followed by iguana (3.49 +/- 0.12 g/100 g) and beef (2.57 +/- 0.20 g/100 g). Ash and most individual minerals were more concentrated in iguana meat, except for K and Zn that were more abundant in beef samples. Non-significant differences in Mg, Na, Cu or Mn contents were detected between chicken and beef samples. It was concluded that iguana meat could be an alternate source of protein and minerals as compared to those of traditional meat species.

Analysis of Variance↗
PubMed1999

Identification of a linear epitope of interferon-alpha2b recognized by neutralizing monoclonal antibodies.

Four monoclonal antibodies (mAbs) directed against the recombinant human interferon-alpha2b (IFN-alpha2b) were used as probes to study the interaction of the IFN molecule to its receptors. The [125I]IFN-alpha2b binding to immobilized mAbs was completely inhibited by IFN-alpha2b and IFN-alpha2a but neither IFNbeta nor IFNgamma showed any effect. Gel-filtration HPLC of the immune complexes formed by incubating [125I]IFN-alpha2b with paired mAbs revealed the lack of simultaneous binding of two different antibodies to the tracer, suggesting that all mAbs recognize the same IFN antigenic domain. Furthermore, the mAbs were also able to neutralize the IFN-alpha2b anti-viral and anti-proliferative activities as well as [125I]IFN-alpha2b binding to WISH cell-membranes. As [125I]mAbs did not recognize IFN exposed epitopes in the IFN:receptor complexes, mAb induction of a conformational change in the IFN binding domain impairing its binding to receptors was considered unlikely. In order to identify the IFN region recognized by mAbs, IFN-alpha2b was digested with different proteolytic enzymes. Immunoreactivity of the resulting peptides was examined by Western blot and their sequences were established by Edman degradation after blotting to poly(vinylidene difluoride) membranes. Data obtained indicated that the smallest immunoreactive region recognized by mAbs consisted of residues 107-132 or 107-146. As this zone includes the sequence 123-140, which has been involved in the binding to receptors, and our mAbs did not show an allosteric behaviour, it is concluded that they are directed to overlapping epitopes located close to or even included in the IFN binding domain.

Amino Acid Sequence↗
PubMed1999

Guanidinium-based potentiometric SO2 gas sensor.

An SO2 gas sensor was developed by using a hydrogen sulfite-selective electrode positioned behind a gas-permeable membrane (GPM). The hydrogen sulfite-selective electrode was prepared by incorporating a multicyclic guanidinium ionophore in a plasticized poly(vinyl chloride) membrane. This gas sensor presents important advantages over the conventional Severinghaus-type SO2 gas sensor that contains a pH electrode immersed in an internal solution behind the GPM. The Severinghaus gas sensor suffers interferences from weak acids that can cross the GPM as gases and change the pH of the internal solution. In contrast, in the proposed sensor, the excellent selectivity of the HSO3- electrode and the ability of the GPM to discriminate gaseous from nongaseous species combine to generate the most selective potentiometric SO2 gas sensor reported to date.

Air Pollutants↗
PubMed1999

Complex regulation of prothymosin alpha in mammary tumors arising arising in transgenic mice.

Expression of prothymosin alpha (PTA) has been related to cell proliferation, both normal and pathological. PTA has also been proposed to be a target of the c-myc protooncogene. To study PTA mRNA levels during pathological cell growth, and especially the effect of the activation of specific oncogenes on PTA expression, we have studied its expression in tumors that arise in transgenic mice. We found high PTA levels in mammary tumors arising in c-myc, c-neu, and v-ras transgenic mice. Levels of this protein were variable between different tumors, and there is a differential regulation of PTA respect to other putative c-myc target genes, such as Ornithine Decarboxylase (ODC). Furthermore, expression of PTA is not absolutely dependent of c-myc expression, as shown by MYC depletion experiments performed with antisense oligonucleotides. We conclude that regulation of PTA in these tumors is complex and depends on more than a single activated oncogene.

Animals↗