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F Lopez

Publications and source records attributed to F Lopez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sulfinyl-directed diastereoselective

Introduction of a homochiral p-tolylsulfinyl group at an appropriate position in the alkene accelerates the thermal [5C + 2C] intramolecular cycloaddition to beta-silyloxy-gamma-pyrones and, most importantly, leads to excellent levels of diastereodifferentiation. The resulting adducts can be easily desulfinylated to give optically active 8-oxabicyclic[3.2.1]octane intermediates which by virtue of their rich functionalization might be susceptible to elaboration into enantiomerically pure natural products containing seven-membered carbocycles and tetrahydrofurans.

Journal Article↗
PubMed2000

Effect of inhaled nitric oxide in combination with almitrine on ventilation-perfusion distributions in experimental lung injury.

OBJECTIVE: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V(A)/Q) ratio. DESIGN: Prospective, controlled animal study. SETTING: Animal research facility of a university hospital. INTERVENTIONS: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 microg/kg per min ALM, 3) 1 microg/ kg per min ALM. For each condition, gas exchange, hemodynamics and V(A)/Q distributions were analyzed using the multiple inert gas elimination technique (MIGET). MEASUREMENT AND RESULTS: With NO + ALM, arterial oxygen partial pressure (PaO2) increased from 63 +/- 18 mmHg to 202 +/- 97 mmHg while intrapulmonary shunt decreased from 50 +/- 15 % to 26 +/- 12% and blood flow to regions with a normal V(A)/Q ratio increased from 49 +/- 16 % to 72 +/- 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05). CONCLUSIONS: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V(A)/Q relationships.

Administration, Inhalation↗
PubMed2000

L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets.

L-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of L-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL + LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of L-carnitine on this parameter. The reduction of total cholesterol in VLDL + LDL particles in animals fed a cholesterol-rich diet plus L-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. L-Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18 fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of L-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL + LDL particles.

Animals↗
PubMed2000

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

OBJECTIVE: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. MATERIALS AND METHODS: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design. RESULTS: Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Adult↗
PubMed2000

Reverse transcriptase-polymerase chain reaction validation of 25 "orphan" genes from Escherichia coli K-12 MG1655.

Despite the accumulation of sequence information sampling from a broad spectrum of phyla, newly sequenced genomes continue to reveal a high proportion (50%-30%) of "uncharacterized" genes, including a significant number of strictly "orphan" genes, i.e., putative open reading frames (ORFs) without any resemblance to previously determined protein-coding sequences. Most genes found in databases have only been predicted by computer methods and have never been experimentally validated. Although theoretical evolutionary arguments support the reality of genes when homologs are found in a variety of distant species, this is not the case for orphan genes. Here, we report the direct reverse transcriptase-polymerase chain reaction assay of 25 strictly orphan ORFs of Escherichia coli. Two growth conditions, exponential and stationary phases, were tested. Transcripts were identified for a total of 19 orphan genes, with 2 genes found to be expressed in only one of the two growth conditions. Our results suggest that a vast majority of E. coli ORFs presently annotated as "hypothetical" correspond to bona fide genes. By extension, this implies that randomly occurring "junk" ORFs have been actively counter selected during the evolution of the dense E. coli genome.

Escherichia coli↗
PubMed2000

Comparison of dosimetric characteristics of Siemens virtual and physical wedges.

Dosimetric properties of Virtual Wedge (VW) and physical wedge (PW) in 6 and 23 MV photon beams from a Siemens Primus linear accelerator, including wedge factors, depth doses, dose profiles, peripheral doses and surface doses, are compared. While there is a great difference in absolute values of wedge factors, VW factors (VWFs) and PW factors (PWFs) have a similar trend as a function of field size. PWFs have a stronger depth dependence than VWF due to beam hardening in PW fields. VW dose profiles in the wedge direction, in general, match very well with PW, except in the toe area of large wedge angles with large field sizes. Dose profiles in the nonwedge direction show a significant reduction in PW fields due to off-axis beam softening and oblique filtration. PW fields have significantly higher peripheral doses than open and VW fields. VW fields have similar surface doses as the open fields while PW fields have lower surface doses. Surface doses for both VW and PW increase with field size and slightly with wedge angle. For VW fields with wedge angles 45 degrees and less, the initial gap up to 3 cm is dosimetrically acceptable when compared to dose profiles of PW. VW fields in general use less monitor units than PW fields.

Humans↗
PubMed2000

Implementation and verification of virtual wedge in a three-dimensional radiotherapy planning system.

Virtual Wedge (VW) is a Siemens treatment modality which generates wedge-shaped dose distributions by moving a collimator jaw from closed to open at a constant speed while varying the dose rate in every 2 mm jaw position. In this work, the implementation and verification of VW in a radiotherapy treatment planning (RTP) system is presented. The VW implementation models the dose delivered by VW using the Siemens monitor units (MU) analytic formalism which determines the number of MU required to generate a wedge-fluence profile at points across the VW beam. For any set of treatment parameters, the VW algorithm generates an "intensity map" that is used to model the modification of fluence emanating from the collimator. The intensity map is calculated as the ratio of MU delivered on an axis point, divided by the monitor units delivered on the central-axis MU(0). The dose calculation is then performed using either the Clarkson or Convolution/ Superposition algorithms. The VW implementation also models the operational constraints for the delivery of VW due to dose rate and jaw speed limits. Dose verifications with measured profiles were performed using both the Clarkson and Convolution/Superposition algorithms for three photon beams; Siemens Primus 6 and 23 MV, and Mevatron MD 15 MV. Agreement within 2% or 2 mm was found between calculated and measured doses, over a large set of test cases, for 15, 30, 45, and 60 degree symmetric and asymmetric VW fields, using the manufacturer's supplied mu and c values for each beam.

Algorithms↗
PubMed1999

Gut mucosal atrophy after a short enteral fasting period in critically ill patients.

PURPOSE: The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. MATERIALS AND METHODS: Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. RESULTS: We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. CONCLUSIONS: We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Adult↗
PubMed1999

The yeast inositol monophosphatase is a lithium- and sodium-sensitive enzyme encoded by a non-essential gene pair.

Inositol monophosphatases (IMPases) are lithium-sensitive enzymes that participate in the inositol cycle of calcium signalling and in inositol biosynthesis. Two open reading frames (YHR046c and YDR287w) with homology to animal and plant IMPases are present in the yeast genome. The two recombinant purified proteins were shown to catalyse inositol-1-phosphate hydrolysis sensitive to lithium and sodium. A double gene disruption had no apparent growth defect and was not auxotroph for inositol. Therefore, lithium effects in yeast cannot be explained by inhibition of IMPases and inositol depletion, as suggested for animal systems. Overexpression of yeast IMPases increased lithium and sodium tolerance and reduced the intracellular accumulation of lithium. This phenotype was blocked by a null mutation in the cation-extrusion ATPase encoded by the ENA1/PMR2A gene, but it was not affected by inositol supplementation. As overexpression of IMPases increased intracellular free Ca2+, it is suggested that yeast IMPases are limiting for the optimal operation of the inositol cycle of calcium signalling, which modulates the Ena1 cation-extrusion ATPase.

Amino Acid Sequence↗
PubMed1999

Large-scale statistical analyses of rice ESTs reveal correlated patterns of gene expression.

Large, publicly available collections of expressed sequence tags (ESTs) have been generated from Arabidopsis thaliana and rice (Oryza sativa). A potential, but relatively unexplored application of this data is in the study of plant gene expression. Other EST data, mainly from human and mouse, have been successfully used to point out genes exhibiting tissue- or disease-specific expression, as well as for identification of alternative transcripts. In this report, we go a step further in showing that computer analyses of plant EST data can be used to generate evidence of correlated expression patterns of genes across various tissues. Furthermore, tissue types and organs can be classified with respect to one another on the basis of their global gene expression patterns. As in previous studies, expression profiles are first estimated from EST counts. By clustering gene expression profiles or whole cDNA library profiles, we show that genes with similar functions, or cDNA libraries expected to share patterns of gene expression, are grouped together. Promising uses of this technique include functional genomics, in which evidence of correlated expression might complement (or substitute for) those of sequence similarity in the annotation of anonymous genes and identification of surrogate markers. The analysis presented here combines the application of a correlation-based clustering method with a graphical color map allowing intuitive visualization of patterns within a large table of expression measurements.

Contig Mapping↗
PubMed1998

sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1.

We have previously reported in Chinese hamster ovary (CHO) cells expressing sst2 that activation of the sst2 somatostatin receptor inhibits insulin-induced cell proliferation by a mechanism involving stimulation of a tyrosine phosphatase activity. Here we show that the tyrosine phosphatase SHP-1 was associated with the insulin receptor (IR) at the basal level. Activation of IR by insulin resulted in a rapid and transient increase of tyrosine phosphorylation of IR, its substrates IRS-1 and Shc, and also of SHP-1. This was then followed by a rapid dephosphorylation of these molecules, which was related to the insulin-induced increase of SHP-1 association to IR and of SHP-1 activity. On the other hand, addition to insulin of the somatostatin analogue, RC160, resulted in a higher and faster increase of SHP-1 association to IR directly correlated with an inhibition of phosphorylation of IR and its substrates, IRS-1 and Shc. RC160 also induced a higher and more sustained increase in SHP-1 activity. Furthermore, RC160 completely suppressed the effect of insulin on SHP-1 phosphorylation. Finally, in CHO cells coexpressing sst2 and a catalytically inactive mutant SHP-1, insulin as well as RC160 could no longer stimulate SHP-1 activity. Overexpression of the SHP-1 mutant prevented the insulin-induced signaling to be terminated by dephosphorylation of IR, suppressed the inhibitory effect of RC160 on insulin-induced IR phosphorylation, and abolished the cell proliferation modulation by insulin and RC160. Our results suggest that SHP-1 plays a role in negatively modulating insulin signaling by association with IR. Furthermore, somatostatin inhibits the insulin-induced mitogenic signal by accelerating and amplifying the effect of SHP-1 on the termination of the insulin signaling pathway.

Animals↗
PubMed1998

Culture-negative endocarditis caused by Bartonella henselae.

A 4-year-old girl presented with clinical evidence of infective endocarditis involving her aortic valve, but blood cultures were sterile. Serologic studies and analysis of resected valve by immunohistochemistry and polymerase chain reaction established the diagnosis of Bartonella henselae endocarditis. Clinicians should be aware that B. henselae can cause apparent culture-negative endocarditis in children.

Antibodies, Bacterial↗
PubMed1998

Alternate polyadenylation in human mRNAs: a large-scale analysis by EST clustering.

Alternate polyadenylation is an important post-transcriptional regulatory process now open to large-scale analysis by use of cDNA databases. We clustered 164,000 expressed sequence tags (ESTs) into approximately 15,000 groups and aligned each group to a putative mRNA 3' end. By use of stringent criteria to discard artifactual mRNA extremities, clear evidence for alternate polyadenylation was obtained in 189 of the 1000 EST clusters studied. A number of previously unreported polyadenylation sites were identified, together with possible instances of tissue-specific differential polyadenylation. This study demonstrates that, besides quantitative aspects of gene expression, the distribution of alternate mRNA forms can be analyzed through EST sampling.

Computational Biology↗
PubMed1997

The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling.

Activation of the somatostatin receptor sst2, a member of the Gi protein-coupled receptor family, results in the stimulation of a protein-tyrosine phosphatase activity involved in the sst2-mediated growth inhibitory signal. Here, we report that SHP-1, a cytoplasmic protein-tyrosine phosphatase containing two Src homology 2 domains constitutively associated with sst2 as evidence by coprecipitation of SHP-1 protein with sst2, in Chinese hamster ovary cells coexpressing sst2 and SHP-1. Activation of sst2 by somatostatin resulted in a rapid dissociation of SHP-1 from sst2 accompanied by an increase of SHP-1 activity. SHP-1 was phosphorylated on tyrosine in control cells and somatostatin induced a rapid and transient dephosphorylation on tyrosine residues of the enzyme. Stimulation of SHP-1 activity by somatostatin was abolished by pertussis toxin pretreatment of cells. Gialpha3 was specifically immunoprecipitated by anti-sst2 and anti-SHP-1 antibodies, and somatostatin induced a rapid dissociation of Gialpha3 from sst2, suggesting that Gialpha3 may be involved in the sst2.SHP-1 complexes. Finally, somatostatin inhibited the proliferation of cells coexpressing sst2 and SHP-1, and this effect was suppressed in cells coexpressing sst2 and the catalytic inactive SHP-1 (C453S mutant). Our data identify SHP-1 as the tyrosine phosphatase associated with sst2 and demonstrate that this enzyme may be an initial key transducer of the antimitogenic signaling mediated by sst2.

Animals↗
PubMed1997

Iron triggers a rapid induction of ascorbate peroxidase gene expression in Brassica napus.

In plants, only ferritin gene expression has been reported to be iron-dependent. Here it is demonstrated that an iron overload of Brassica napus seedlings causes a large and rapid accumulation of ascorbate peroxidase transcripts, a plant-specific hydrogen peroxide-scavenging enzyme. This result documents a novel link between iron metabolism and oxidative stress. The ascorbate peroxidase mRNA abundance was not modified by reducing agents like N-acetyl cysteine, glutathione and ascorbate or by pro-oxidants such as hydrogen peroxide or diamide. Furthermore, the iron-induced ascorbate peroxidase mRNA accumulation was not antagonized by N-acetyl cysteine. Abscisic acid had no effect on the ascorbate peroxidase gene expression. Taken together these results suggest that iron-mediated expression of ascorbate peroxidase gene occurs through a signal transduction pathway apparently different from those already described for plant genes responsive to oxidative stress.

Abscisic Acid↗