188 results on '"R. Laguna"'
Search Results
152. The search for a curative cell therapy in Parkinson's disease.
- Author
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Laguna Goya R, Tyers P, and Barker RA
- Subjects
- Animals, Cell Differentiation physiology, Cell Proliferation, Cell Transplantation methods, Cell- and Tissue-Based Therapy trends, Humans, Stem Cells physiology, Cell- and Tissue-Based Therapy methods, Neurons physiology, Parkinson Disease therapy
- Abstract
Parkinson's disease (PD) is a neurodegenerative disorder, characterised by the progressive loss of dopaminergic neurons in the substantia nigra, and typically treated by dopamine replacement. This treatment, although very effective in the early stages of the disease, is not curative and has side-effects. As such there has been a search for a more definitive treatment for this condition, which has mainly concentrated on replacing the lost neurons with neural grafts. Possible cell sources for replacement range from autologous grafts of dopamine secreting cells to allografts of fetal ventral mesencephalon and neural precursor cells derived from fetal tissue or embryonic stem cells. Some of these cells have been the subject of clinical trials, which to date have produced disparate outcomes. Therefore, whilst cell therapies remain a promising treatment for PD, there is need for further refinement of the techniques involved in this experimental procedure, before any new trials in patients are undertaken.
- Published
- 2008
- Full Text
- View/download PDF
153. Total hip arthroplasty in paralytic dislocation from poliomyelitis.
- Author
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Laguna R and Barrientos J
- Subjects
- Adult, Arthroplasty, Replacement, Hip instrumentation, Arthroplasty, Replacement, Hip methods, Female, Humans, Treatment Outcome, Hip Joint surgery, Hip Prosthesis, Joint Dislocations etiology, Joint Dislocations surgery, Paralysis etiology, Paralysis surgery, Poliomyelitis complications, Poliomyelitis surgery
- Abstract
This article presents a case of a patient with degenerative hip disease in paralytic dislocation by poliomyelitis. Poliomyelitis is an acute infection disease caused by a group of neurotrophic viruses, which has a special affinity by the anterior horns cells of the spinal cord and for certain motor nuclei of the brain stem. Paralysis is a flaccid type and characteristically paralysis is asymmetrical. It is said that the joints of the affected limb by poliomyelitis are protected from the development of osteoarthritis. Hip dislocation in poliomyelitis is an acquired deformity caused by flaccid paralysis and the resulting muscular imbalance. In young children, when the gluteus maximus and medius muscles are paralyzed and the hip flexors and adductors are of normal strength, eventual luxation of the hip is almost inevitable. Hip osteoarthritis in a limb with poliomyelitis is an unusual entity because these limbs do not support excessive loads. In patients who present with the residual effects of poliomyelitis including degenerative disease and hip dysplastic, surgery is one of the most difficult challenges faced by reconstructive surgeons. In such cases, surgeons should attempt to optimize the component position and choice, surgical approach, and soft tissue tensioning because stability of the prosthesis can be problematic.
- Published
- 2008
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154. 2-Substituted 4-, 5-, and 6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones and 2-substituted 4,5-bis[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones as potent platelet aggregation inhibitors: design, synthesis, and SAR studies.
- Author
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Meyers C, Yáñez M, Elmaatougi A, Verhelst T, Coelho A, Fraiz N, Lemière GL, García-Mera X, Laguna R, Cano E, Maes BU, and Sotelo E
- Subjects
- Drug Design, Platelet Aggregation Inhibitors chemical synthesis, Pyridazines chemical synthesis, Structure-Activity Relationship, Platelet Aggregation Inhibitors chemistry, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemistry, Pyridazines pharmacology
- Abstract
A set of regioisomeric 2-substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1-yl fragment at either position 4, 5 or 6 and 2-substituted pyridazin-3(2H)-ones containing the same fragment both at positions 4 and 5 have been synthesized and evaluated as antiplatelet agents. The study allows the identification of a new highly potent platelet aggregation inhibitor (4c).
- Published
- 2008
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155. Design, synthesis, and structure-activity relationships of a novel series of 5-alkylidenepyridazin-3(2H)-ones with a non-cAMP-based antiplatelet activity.
- Author
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Coelho A, Raviña E, Fraiz N, Yáñez M, Laguna R, Cano E, and Sotelo E
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- Alkenes chemistry, Alkenes pharmacology, Blood Platelets drug effects, Drug Design, Humans, In Vitro Techniques, Platelet Aggregation Inhibitors chemistry, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemistry, Pyridazines pharmacology, Stereoisomerism, Structure-Activity Relationship, Alkenes chemical synthesis, Platelet Aggregation Inhibitors chemical synthesis, Pyridazines chemical synthesis
- Abstract
5-alkylidenepyridazin-3-ones with four points of diversity (R2, R6, X, Y) have been synthesized and evaluated as platelet aggregation inhibitors. Several derivatives eliciting antiplatelet activity in the low micromolar range (e.g., 14e, 14k, 14p, 14v, IC50 congruent with 1 microM) were identified. Structure-activity relationships studies on these compounds revealed the key molecular determinants of this new family of antiplatelet agents: (a) two ester groups in the alkoxy moieties; (b) lipophilic substituents at the N2 position of the pyridazin-3-one. The preliminary results of a pharmacological study aimed at determining the mechanism of action of a set of representative compounds revealed that, unlike other pyridazinones, the documented antiplatelet effect is not a consequence of a PDE-III inhibitory activity.
- Published
- 2007
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156. The future of cell therapies in the treatment of Parkinson's disease.
- Author
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Laguna Goya R, Kuan WL, and Barker RA
- Subjects
- Animals, Disease Models, Animal, Dyskinesias etiology, Humans, Mesencephalon embryology, Nerve Regeneration, Parkinson Disease physiopathology, Transplantation, Homologous, Treatment Outcome, Brain Tissue Transplantation adverse effects, Embryonic Stem Cells transplantation, Fetal Tissue Transplantation adverse effects, Mesencephalon transplantation, Mesenchymal Stem Cell Transplantation, Parkinson Disease surgery
- Abstract
Parkinson's disease (PD) is a common neurological disorder of the brain which has as a part of its core pathology the progressive degeneration of the dopaminergic nigrostriatal pathway. Therefore, cell therapies that aim to restore this degenerated dopaminergic network represent a promising strategy in helping to cure PD. In this review, the authors start by discussing the progress of research on the use of fetal ventral mesencephalic (VM) tissue in transplantation therapies in PD, both from the clinical and experimental perspectives. Then the issues pertinent to its adoption in the clinic are discussed, including the ethical and practical problems with its use, the varied composition of VM tissue that is implanted with the graft and how this may account for some of the problems seen in the clinical trials using this tissue, especially graft-induced dyskinesia. Finally other promising sources of tissue for PD cell therapy are described, including mesenchymal and embryonic stem cells, before concluding on what is the best approach to the cellular repair of the parkinsonian brain.
- Published
- 2007
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157. Western blot antibody determination in sera from patients diagnosed with Anisakis sensitization with different antigenic fractions of Anisakis simplex purified by affinity chromatography.
- Author
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Rodero M, Cuéllar C, Chivato T, Mateos JM, and Laguna R
- Subjects
- Animals, Antigens, Helminth isolation & purification, Blotting, Western, Chromatography, Affinity, Humans, Immunoglobulin G immunology, Immunoglobulin M immunology, Sensitivity and Specificity, Anisakiasis diagnosis, Anisakis immunology, Antibodies, Helminth blood, Antigens, Helminth immunology
- Abstract
Using Western blot techniques, the specificities of crude and purified (PAK and PAS) Anisakis simplex antigens were compared against 24 sera from patients diagnosed with Anisakis sensitization. All patients recognized a 60 kDa protein against the A. simplex crude extract, while 37.5% and 12.5% reacted with proteins of 40 and 25 kDa, respectively, when IgG was tested. In the case of IgE determination, 41.6% of sera were negative, while 12.5% and 20.8% appeared to cross-react against Toxocara canis and Ascaris suum, respectively. When the PAK antigen (A. simplex antigen purified by means of a column of IgG anti-A. simplex) was tested, immune recognition towards the 60, 40 and 25 kDa proteins increased in 83.3%, 16.7% and 4.2%, respectively, when the Ig antibodies were tested. In the case of the PAS antigen (PAK antigen purified by means of a column of IgG anti-A. suum), the reaction against the 40 and 25 kDa proteins increased to 45.8% and 25%, respectively, when Ig antibodies were used. Finally, when the EAS antigen (eluted from the anti-A. suum column after PAK purification) was tested, 83.3% of the assayed sera reacted against the 14 kDa protein, when the Ig antibodies, IgG and IgM immunoglobulins were measured. With the IgE determination, the reactions were observed in 41.7% of patients with proteins between 60 and 35 kDa against the PAS antigen. With the EAS antigen, reactive bands of 184, 84 and 14 kDa appeared. In conclusion, in the purification process of the A. simplex larval crude extract, the proteins implicated in cross-reactions with Ascaris and Toxocara were eliminated, with an important concentration of proteins responsible for the induction of specific responses.
- Published
- 2007
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158. ELISA antibody determination in patients with anisakiosis or toxocariosis using affinity chromatography purified antigen.
- Author
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Rodero M, Cuéllar C, Fenoy S, del Aguila C, Chivato T, Mateos JM, and Laguna R
- Subjects
- Animals, Antigens, Helminth immunology, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Immunoglobulin M blood, Immunoglobulin M immunology, Sensitivity and Specificity, Anisakiasis diagnosis, Antigens, Helminth isolation & purification, Chromatography, Affinity, Enzyme-Linked Immunosorbent Assay, Larva Migrans, Visceral diagnosis
- Abstract
One of the fundamental aspects of a parasitic infection diagnosis is the use of adequate antigens to develop specific and sensitive immunoassays. This fact is especially complicated in nematode infection cases because of the high cross-reactivity among different parasites in this group. We performed an evaluation of Anisakis simplex antigens purified by affinity chromatography. We used sera from 38 patients diagnosed with Anisakis sensitization and sera from 35 patients with clinical suspicion of visceral larva migrans (VLM). These sera were assayed by the ELISA method against the crude extracts (CEs) and the purified antigens. When the sera from patients diagnosed with Anisakis sensitization were tested against the A. simplex CE, the IgG was the most abundant immunoglobulin. When the A. simplex larval antigens were purified using a column of IgG anti-A. simplex (PAK) or a column of IgG anti-Ascaris suum (PAS) were tested, we observed a higher diminution in the IgG levels, which coincides with the augmentation of the mean values against the "eluted of Ascaris" (EAS antigen). When the IgE was detected, only 18.4% of the sera reacted with the PAS antigen. We have observed that in the purification process of A. simplex antigen by affinity chromatography, the majority of the proteins that produced cross-reactivity against A. suum and Toxocara canis were eliminated.
- Published
- 2006
- Full Text
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159. Identification of the DNA bases of a DNase I footprint by the use of dye primer sequencing on an automated capillary DNA analysis instrument.
- Author
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Zianni M, Tessanne K, Merighi M, Laguna R, and Tabita FR
- Subjects
- Base Sequence, DNA Primers chemistry, Densitometry, Indicators and Reagents pharmacology, Molecular Sequence Data, Nucleotides chemistry, Plants microbiology, Plasmids metabolism, Polymerase Chain Reaction methods, Promoter Regions, Genetic, Reproducibility of Results, Rhodobacter metabolism, DNA chemistry, Deoxyribonuclease I chemistry, Fluorescent Dyes pharmacology, Sequence Analysis, DNA instrumentation, Sequence Analysis, DNA methods
- Abstract
We have adapted the techniques of DNA footprint analysis to an Applied Biosystems 3730 DNA Analyzer. The use of fluorescently labeled primers eliminates the need for radioactively labeled nucleotides, as well as slab gel electrophoresis, and takes advantage of commonly available automated fluorescent capillary electrophoresis instruments. With fluorescently labeled primers and dideoxynucleotide DNA sequencing, we have shown that the terminal base of each digested fragment may be accurately identified with a capillary-based instrument. Polymerase chain reaction (PCR) was performed with a 6FAM-labeled primer to amplify a typical target promoter region. This PCR product was then incubated with a transcriptional activator protein, or bovine serum albumin as a control, and then partially digested with DNase I. A clone of the promoter was sequenced with the Thermo Sequenase Dye Primer Manual Cycle Sequencing kit (USB) and the FAM-labeled primer. Through the use of Genemapper software, the Thermo sequenase and DNasei digestion products were accurately aligned, providing a ready means to assign correct nucleotides to each peak from the DNA footprint. This method was used to characterize the binding of two different transcriptional activator proteins to their respective promoter regions.
- Published
- 2006
160. Pyridazines part 41: synthesis, antiplatelet activity and SAR of 2,4,6-substituted 5-(3-oxo-3-phenylprop-1-en-1-yl)- or 5-(3-phenylprop-2-enoyl)pyridazin-3(2H)-ones.
- Author
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Crespo A, Meyers C, Coelho A, Yáñez M, Fraiz N, Sotelo E, Maes BU, Laguna R, Cano E, Lemière GL, and Raviña E
- Subjects
- Molecular Structure, Platelet Aggregation Inhibitors chemistry, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemistry, Stereoisomerism, Structure-Activity Relationship, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors chemical synthesis, Pyridazines chemical synthesis, Pyridazines pharmacology
- Abstract
As part of the optimization process of the lead compound I a focussed library of diversely substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1-yl or 3-phenylprop-2-enoyl fragment at position 5 has been obtained and evaluated as antiplatelet agents. The structural modification at positions 2, 6 and 4 of the heterocyclic moiety allowed us to obtain preliminary information on the structure-activity relationship in this family.
- Published
- 2006
- Full Text
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161. Effects of cis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes.
- Author
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Leiro J, Alvarez E, Arranz JA, Laguna R, Uriarte E, and Orallo F
- Subjects
- Animals, Antineoplastic Agents pharmacology, Cyclooxygenase 2, Dinoprostone metabolism, Down-Regulation, Hypoxanthine metabolism, Interferon-gamma pharmacology, Isoenzymes metabolism, Lipopolysaccharides pharmacology, Macrophages, Peritoneal metabolism, Mice, Mice, Inbred BALB C, Multienzyme Complexes antagonists & inhibitors, NADH, NADPH Oxidoreductases antagonists & inhibitors, NADPH Oxidases antagonists & inhibitors, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Prostaglandin-Endoperoxide Synthases metabolism, Rats, Rats, Wistar, Resveratrol, Xanthine Oxidase metabolism, Antioxidants pharmacology, Macrophages, Peritoneal drug effects, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Respiratory Burst drug effects, Stilbenes pharmacology
- Abstract
This study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1-100 microM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10-100 microM significantly reduced RNS production. c-RESV at 1-100 microM was ineffective for scavenging superoxide radicals (O(2)(.-)), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10-100 microM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 microM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-gamma)-treated macrophages. At 10-100 microM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E(2) (PGE(2)) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O(2)(.-)(-) and of the proinflammatory mediators NO(.-) and PGE(2)).
- Published
- 2004
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162. Pyridazines. Part 36: Synthesis and antiplatelet activity of 5-substituted-6-phenyl-3(2H)-pyridazinones.
- Author
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Coelho A, Sotelo E, Fraiz N, Yáñez M, Laguna R, Cano E, and Raviña E
- Subjects
- Humans, Platelet Aggregation drug effects, Platelet Aggregation physiology, Platelet Aggregation Inhibitors chemical synthesis, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemical synthesis, Pyridazines pharmacology
- Abstract
A convenient and efficient palladium-catalysed retro-ene-assisted method has been developed to prepare a series of 5-substituted-6-phenyl-3(2H)-pyridazinones as potential antiplatelet drugs. The most active compounds were those that contain a 3-phenyl-3-oxo-propenyl fragment or a phenylthio group at position 5 of the heterocyclic ring.
- Published
- 2004
- Full Text
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163. Cross-reactivity between Anisakis simplex sensitization and visceral larva migrans by Toxocara canis.
- Author
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Perteguer MJ, Cuéllar C, Guillén JL, Aguila C, Fenoy S, Chivato T, and Laguna R
- Subjects
- Animals, Anisakiasis immunology, Cross Reactions, Diagnosis, Differential, Enzyme-Linked Immunosorbent Assay, Humans, Larva Migrans, Visceral immunology, Reagent Kits, Diagnostic, Anisakiasis diagnosis, Anisakis immunology, Antigens, Helminth immunology, Larva Migrans, Visceral diagnosis, Toxocara canis immunology
- Abstract
The aim of this work was to study cross-reactivity in the diagnosis of two related ascaridosis. Nineteen patients diagnosed with recidivous acute urticaria (RAU) caused by Anisakis simplex and 26 patients diagnosed with visceral larva migrans (VLM) caused by Toxocara canis were studied employing commercial diagnostic kits and "in house" assay kits. Cross-reactivity observed was greater when using "in house" assay kits, suggesting that T. canis excretory-secretory antigens were not only recognized by antibodies from patients with RAU but with greater intensity compared to the A. simplex excretory-secretory antigens.
- Published
- 2003
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164. Pyridazines. Part 31: synthesis and antiplatelet activity of 4,5-disubstituted-6-phenyl-3(2H)-pyridazinones.
- Author
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Sotelo E, Fraiz N, Yáñez M, Laguna R, Cano E, and Raviña E
- Subjects
- Dose-Response Relationship, Drug, Humans, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors chemistry, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemistry, Pyridazines pharmacology, Structure-Activity Relationship, Platelet Aggregation Inhibitors chemical synthesis, Pyridazines chemical synthesis
- Abstract
This paper describes the synthesis and the antiplatelet activity of a series of 4,5-disubstituted-6-phenyl-3(2H)-pyridazinones. Some of these compounds show a dose-dependent activity and were found to be more active than their 5-substituted analogues.
- Published
- 2002
- Full Text
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165. Pyridazines. Part XXIX: synthesis and platelet aggregation inhibition activity of 5-substituted-6-phenyl-3(2H)-pyridazinones. Novel aspects of their biological actions.
- Author
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Sotelo E, Fraiz N, Yáñez M, Terrades V, Laguna R, Cano E, and Raviña E
- Subjects
- 3',5'-Cyclic-AMP Phosphodiesterases, Animals, Blood Platelets drug effects, Blood Platelets metabolism, Calcium metabolism, Cyclic Nucleotide Phosphodiesterases, Type 3, Cytosol chemistry, Dose-Response Relationship, Drug, Guinea Pigs, Humans, Inhibitory Concentration 50, Kinetics, Phosphodiesterase Inhibitors chemical synthesis, Phosphodiesterase Inhibitors pharmacology, Phosphorylation, Platelet Aggregation Inhibitors pharmacology, Pyridazines pharmacology, Structure-Activity Relationship, Platelet Aggregation Inhibitors chemical synthesis, Pyridazines chemical synthesis
- Abstract
A series of 6-phenyl-3(2H)-pyridazinones with a diverse range of substituents in the 5-position have been prepared and evaluated in the search for new antiplatelet agents. A significant dependence of the substituent on the inhibitory effect has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at position 5 of the 6-phenyl-3(2H)-pyridazinone system influences both variations in the antiplatelet activity and the mechanism of action.
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- 2002
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166. Pyridazines. Part 28: 5-alkylidene-6-phenyl-3(2H)-pyridazinones, a new family of platelet aggregation inhibitors.
- Author
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Sotelo E, Fraiz N, Yáñez M, Laguna R, Cano E, Brea J, and Raviña E
- Subjects
- Platelet Aggregation Inhibitors chemistry, Pyridazines chemistry, Structure-Activity Relationship, Platelet Aggregation Inhibitors chemical synthesis, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemical synthesis, Pyridazines pharmacology
- Abstract
The synthesis and anti-platelet activity of several 5-alkylidene-6-phenyl-3(2H)-pyridazinones are described. The most active compounds are those that contain oxygenated functions (COOR, COMe) on the alkylidene fragment (6a, 6b and 6c).
- Published
- 2002
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167. Purification of Anisakis simplex antigen by affinity chromatography.
- Author
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Rodero M, Jiménez A, Chivato T, Laguna R, and Cuéllar C
- Subjects
- Animals, Anisakiasis parasitology, Antibodies, Helminth immunology, Chromatography, Affinity methods, Electrophoresis, Polyacrylamide Gel, Humans, Immune Sera, Immunoblotting, Rabbits, Sensitivity and Specificity, Anisakiasis diagnosis, Anisakis immunology, Antibodies, Helminth blood, Antigens, Helminth immunology, Antigens, Helminth isolation & purification
- Abstract
In order to improve the specificity and sensitivity of the techniques for the diagnosis of human anisakidosis, a method of affinity chromatography for the purification of species-specific antigens from Anisakis simplex third-stage larvae (L3) has been developed. New Zealand rabbits were immunized with A. simplex or Ascaris suum antigens or inoculated with Toxocara canis embryonated eggs. The IgG-specific antibodies were isolated by means of protein A-Sepharose CL-4B bead columns. IgG anti-Anisakis simplex, anti-Ascaris suum and anti-T. canis were coupled to CNBr-activated Sepharose 4B. For the purification of the larval Anisakis simplex antigens, it was loaded into the anti-A. simplex column and bound antigens were eluted. For the elimination of the epitopes responsible for the cross-reactions, the A. simplex-specific proteins were loaded into the anti-Ascaris suum and anti- T. canis columns. To prove the specificity of the isolated proteins, immunochemical analyses by polyacrylamide gel electrophoresis and immunoblotting were carried out. Likewise, immunoaffinity columns were prepared using specific IgG from patients with Anisakis simplex sensitization, previously diagnosed by fluoro-enzymo-immunoassay. The protein patterns of antigen after purification by the human columns were similar to those obtained using the rabbit columns.
- Published
- 2001
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168. Induction of phase variation events in the life cycle of the marine coccolithophorid Emiliania huxleyi.
- Author
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Laguna R, Romo J, Read BA, and Wahlund TM
- Subjects
- Culture Media, DNA analysis, DNA genetics, Darkness, Flow Cytometry, Light, Polymerase Chain Reaction, Eukaryota genetics, Eukaryota growth & development, Gene Expression Regulation, Seawater microbiology
- Abstract
Emiliania huxleyi is a unicellular marine alga that is considered to be the world's major producer of calcite. The life cycle of this alga is complex and is distinguished by its ability to synthesize exquisitely sculptured calcium carbonate cell coverings known as coccoliths. These structures have been targeted by materials scientists for applications relating to the chemistry of biomedical materials, robust membranes for high-temperature separation technology, lightweight ceramics, and semiconductor design. To date, however, the molecular and biochemical events controlling coccolith production have not been determined. In addition, little is known about the life cycle of E. huxleyi and the environmental and physiological signals triggering phase switching between the diploid and haploid life cycle stages. We have developed laboratory methods for inducing phase variation between the haploid (S-cell) and diploid (C-cell) life cycle stages of E. huxleyi. Plating E. huxleyi C cells on solid media was shown to induce phase switching from the C-cell to the S-cell life cycle stage, the latter of which has been maintained for over 2 years under these conditions. Pure cultures of S cells were obtained for the first time. Laboratory conditions for inducing phase switching from the haploid stage to the diploid stage were also established. Regeneration of the C-cell stage from pure cultures of S cells followed a predictable pattern involving formation of large aggregations of S cells and the subsequent production of cultures consisting predominantly of diploid C cells. These results demonstrate the ability to manipulate the life cycle of E. huxleyi under controlled laboratory conditions, providing us with powerful tools for the development of genetic techniques for analysis of coccolithogenesis and for investigating the complex life cycle of this important marine alga.
- Published
- 2001
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169. Vertebral hemangioma mimicking a metastatic bone lesion in well-differentiated thyroid carcinoma.
- Author
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Laguna R, Silva F, Vazquez-Sellés J, Orduña E, and Flores C
- Subjects
- Carcinoma, Papillary diagnostic imaging, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Iodine Radioisotopes, Lymph Node Excision, Lymphatic Metastasis, Middle Aged, Neoplasm Staging, Radionuclide Imaging, Radiopharmaceuticals, Spinal Neoplasms secondary, Thyroidectomy, Tomography, X-Ray Computed, Whole-Body Counting, Carcinoma, Papillary secondary, Hemangioma diagnostic imaging, Spinal Neoplasms diagnostic imaging, Thoracic Vertebrae diagnostic imaging, Thyroid Neoplasms pathology
- Abstract
The authors report a case of abnormal accumulation of I-131 in a thoracic vertebra in a patient with a well-differentiated thyroid carcinoma. The presumptive diagnosis was metastatic bone disease. Further diagnostic work-up confirmed a benign bone lesion. Bone metastasis, when shown on I-131 whole-body scintigraphy, usually supports a change in the staging and therapeutic approach to a patient with thyroid carcinoma. The authors believe that, although an infrequent lesion, the differential diagnosis of abnormal accumulation of I-131 in the body of a vertebra in patients with well-differentiated thyroid carcinoma should raise the possibility of a benign hemangioma. Complete work-up of the suggested bone metastatic lesion should be performed before tumor restaging and I-131 therapy is recommended.
- Published
- 2000
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170. Specific and total IgE in patients with recurrent, acute urticaria caused by Anisakis simplex.
- Author
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Perteguer MJ, Chivato T, Montoro A, Cuéllar C, Mateos JM, and Laguna R
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Animals, Anisakiasis complications, Anisakiasis diet therapy, Female, Fishes parasitology, Humans, Male, Middle Aged, Reagent Kits, Diagnostic, Recurrence, Skin Tests, Urticaria diet therapy, Urticaria etiology, Anisakiasis immunology, Anisakis immunology, Antigens, Helminth immunology, Immunoglobulin E immunology, Urticaria immunology
- Abstract
Titres of parasite-specific IgE were investigated in 19 patients thought to have recurrent, acute urticaria caused by sensitization to Anisakis simplex (Dujardin, 1845), before and after they were placed on a fish-free diet. Patients with other allergic disease and those being treated with corticosteroids or antihistaminics were excluded. Skin-prick tests were carried out with A. simplex extract, and blue- and white-fish extracts. The CAP system (Pharmacia), a commercial test kit developed for the assay of food-specific IgE, was used to monitor serum concentrations of total IgE and antigen-specific IgE against Anisakis, Ascaris, Echinococcus, Toxocara, tuna, salmon, shrimp, mussel and cod. Before going on a fish-free diet, the 19 patients had CAP scores against A. simplex of 5 (three cases), 3 (seven) or 2 (nine). After a mean of 120 days on the diet, the scores against A. simplex were unchanged in 15 of the cases, reduced in three [from 5 to 4 (one case) or from 2 to 0 (two cases)] and increased in one (from 2 to 3). Most (16) of the patients no longer had any urticaria and the others reported significant reductions in the intensity and frequency of their symptoms.
- Published
- 2000
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171. Pyridazines. XVIII. 6-Aryl-3(2H)-pyridazinones inhibit calcium influx in stimulated platelets.
- Author
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Montero-Lastres A, Fraiz N, Laguna R, Cano E, Estevez I, and Raviña E
- Subjects
- Blood Platelets drug effects, Dose-Response Relationship, Drug, Drug Interactions, Humans, In Vitro Techniques, Ionomycin pharmacology, Platelet Aggregation Inhibitors pharmacology, Thrombin pharmacology, Blood Platelets metabolism, Calcium metabolism, Platelet Aggregation drug effects, Pyridazines pharmacology
- Abstract
6-Phenyl-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone (1) and 6-thienyl-5-hydroxymethyl-4,5-dihydro-3(2H)-pyridazinone (2) inhibit platelet aggregation induced by thrombin (IC50 = 0.25 and 0.26 mM, respectively) or by the calcium ionophore ionomycin (IC50 = 0.42 and 0.43 mM, respectively). Pyridazinones 1 and 2 also show concentration-dependent attenuation of the increases in platelet cytosolic free calcium concentration induced by thrombin and ionomycin, suggesting that their antiaggregatory activity may be due to their capacity to inhibit the passage of calcium through the cytoplasmic membrane. This effect may be implicated in other pharmacological activities of 6-aryl-5-substituted-pyridazinones.
- Published
- 1999
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172. AM1 theoretical study, synthesis and biological evaluation of some benzofuran analogues of anti-inflammatory arylalkanoic acids.
- Author
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Santana L, Teijeira M, Uriarte E, Teran C, Liñares B, Villar R, Laguna R, and Cano E
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal pharmacology, Benzofurans pharmacology, Cyclooxygenase Inhibitors chemical synthesis, Humans, Molecular Conformation, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Benzofurans chemical synthesis
- Abstract
Using the semi-empirical quantum-mechanical method AM1, the molecular geometries of the arylalkanoic acids, indomethacin, naproxen and ibuprofen, were optimized and their frontier orbital charge distributions evaluated. Then, these molecular parameters were compared in order to identify structure-activity relationships and, on the basis of these, four benzofuran-3-acetic acids were designed as potential non-steroidal anti-inflammatory agents, and rapidly synthesized by a novel and easily generalized route. Notwithstanding the structural similarities between the synthesized compounds and the anti-inflammatory arylalkanoic acids, these compounds did not appreciably inhibit human platelet cyclooxygenase in vitro.
- Published
- 1999
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173. Technetium-99m-MAG3 in early identification of pyelonephritis in children.
- Author
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Laguna R, Silva F, Orduña E, Conway JJ, Weiss S, and Calderon C
- Subjects
- Child, Female, Humans, Male, Radionuclide Imaging, Retrospective Studies, Time Factors, Kidney Cortex diagnostic imaging, Organotechnetium Compounds, Pyelonephritis diagnostic imaging, Radiopharmaceuticals, Sugar Acids, Technetium Tc 99m Mertiatide
- Abstract
Unlabelled: The purpose of this study was to determine whether 99mTc-mercaptotriacetylglycine (MAG3) can substitute for 99mTc-glucoheptonate (GH) in the detection of pyelonephritis., Methods: One hundred thirty renal scintigraphies were evaluated retrospectively in 38 children (21% boys, 79% girls; age range 1 mo-21 yr; mean age 7.2 yr) referred for evaluation during an acute clinical urinary tract infection and for follow-up studies. Twelve topographical regions were designated on each kidney. Each area was graded for severity of decreased radionuclide localization: mild (Grade 1), moderate (Grade 2) or marked (Grade 3). Early posterior views of MAG3 studies were compared to delayed posterior GH images. In all patients, both studies were performed on the same day., Results: Eighty-two studies were performed during an acute clinical infection and 48 were performed as follow-up. Seventy-seven percent of the studies had focal cortical lesions. Of all the cortical lesions identified by GH, MAG3 detected 74% (match lesions). A comparable percentage of lesions was identified in each region by both studies. GH scintigraphy detected 261 lesions (63 Grade 1, 149 Grade 2 and 49 Grade 3), and MAG3 detected 201 lesions (37 Grade 1, 117 Grade 2 and 47 Grade 3). MAG3 was unable to recognize 60 lesions identified by GH studies in 11 patients (mismatch lesions). Of these, 41% (26 of 63) were Grade 1, 21% (32 of 149) were Grade 2 and 4% (2 of 49) were Grade 3. In three cases, MAG3 identified lesions not seen by GH (reverse mismatch); all had acute symptomatic infection., Conclusion: These data document that MAG3 in the early phase of the study (1-2 min) can detect Grade 2 to Grade 3 cortical lesions in patients with pyelonephritis, but it is less effective in detecting Grade 1 lesions.
- Published
- 1998
174. Indications for use of the long Gamma nail.
- Author
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Rodriguez Alvarez J, Casteleiro Gonzolez C, Laguna Aranda R, Ferrer Blanco M, and Cuervo Dehesa M
- Subjects
- Adult, Aged, Aged, 80 and over, Fractures, Spontaneous surgery, Humans, Middle Aged, Retrospective Studies, Bone Nails, Femoral Fractures surgery, Fracture Fixation, Intramedullary instrumentation, Hip Fractures surgery
- Abstract
A retrospective analysis of 42 patients treated by intramedullary nailing with the Gamma nail with a mean followup of 22.4 months is reported. The indications for the use of this nail were subtrochanteric fractures in 31 cases, diaphyseal femoral fractures in 10 cases, and segmental fracture in one case. Seven cases of the diaphyseal fractures were renailings for a previously placed nail. There was one pathologic fracture in the subtrochanteric group and three in the diaphyseal group. The indications of this new technique and its complications are analyzed.
- Published
- 1998
175. Osteochondritis dissecans of the talus during childhood and adolescence.
- Author
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Higuera J, Laguna R, Peral M, Aranda E, and Soleto J
- Subjects
- Adolescent, Cartilage, Articular, Child, Female, Follow-Up Studies, Humans, Male, Osteochondritis Dissecans diagnosis, Osteochondritis Dissecans epidemiology, Osteotomy, Radiography, Treatment Outcome, Osteochondritis Dissecans therapy, Talus diagnostic imaging
- Abstract
Between 1985 and 1996, our Service treated 18 cases of osteochondritis dissecans of the talus in children and adolescents. The lesion is more frequent during childhood than previously thought. Different theories about the etiology of the lesion and the various treatments used are discussed. The outcome was satisfactory in most cases. We consider that, with the exception of type IV Berndt and Harty lesions, preliminary treatment should be conservative, which gave good results in our study. Surgical treatment should be reserved for patients with an unsatisfactory evolution with orthopaedic treatment, with lesions with thick sclerotic edges, or for patients with loose intraarticular fragments.
- Published
- 1998
176. Thrombomodulin modulates the mitogenic response to thrombin of human umbilical vein endothelial cells.
- Author
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Lafay M, Laguna R, Le Bonniec BF, Lasne D, Aiach M, and Rendu F
- Subjects
- Antibodies, Monoclonal pharmacology, Cells, Cultured, Endothelium, Vascular cytology, Hirudins analogs & derivatives, Hirudins pharmacology, Humans, Macromolecular Substances, Mitosis, Models, Biological, Oligopeptides pharmacology, Peptide Fragments pharmacology, Prostaglandins F metabolism, Recombinant Proteins pharmacology, Thrombomodulin antagonists & inhibitors, Thrombomodulin immunology, Umbilical Veins, Endothelium, Vascular drug effects, Mitogens pharmacology, Thrombin pharmacology, Thrombomodulin physiology
- Abstract
Thrombin interacts with its receptor and thrombomodulin on endothelial cells. We evaluated the respective roles of these two proteins on human umbilical vein endothelial cell (HUVEC) growth by comparing thrombin, S195A (a mutant thrombin in which the serine of the charge stabilizing system had been replaced by alanine), and the receptor activating peptide (TRAP). Thrombin and TRAP induced DNA synthesis (half maximal cell proliferation with 5 nM and 25 microM, respectively), whereas S195A thrombin was inactive, inferring that growth is mediated through the thrombin receptor. Surprisingly, cells stimulated by TRAP exhibited a maximal proliferation twice greater than that obtained with thrombin. Combination of thrombin and TRAP resulted in a mitogenic response higher than by thrombin alone, but lower than by TRAP alone. The role of thrombomodulin was evaluated by adding an anti-thrombomodulin antibody, which prevents formation of the thrombin-thrombomodulin complex. Antibody did not interfere with cell proliferation induced by TRAP, but enhanced that induced by thrombin. We conclude that formation of the thrombin-thrombomodulin complex restrains HUVEC proliferation mediated through the thrombin receptor.
- Published
- 1998
177. Pyridazines. XIII. Synthesis of 6-aryl-5-oxygenated substituted-3(2H)-pyridazinones and evaluation as platelet aggregation inhibitors.
- Author
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Laguna R, Rodriguez-Liñares B, Cano E, Estevez I, Raviña E, and Sotelo E
- Subjects
- Adenosine Diphosphate pharmacology, Animals, Collagen pharmacology, Evaluation Studies as Topic, Male, Platelet Aggregation drug effects, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Thrombin pharmacology, Platelet Aggregation Inhibitors chemical synthesis, Platelet Aggregation Inhibitors pharmacology, Pyridazines chemical synthesis, Pyridazines pharmacology, Pyridones chemical synthesis, Pyridones pharmacology
- Abstract
Several 6-aryl-5-oxygenated substituted pyridazinones have been synthesized and evaluated in vitro for inhibition of platelet aggregation induced by adenosine 5'-diphosphate (ADP), thrombin and collagen. All the tested compounds (except 8 and 9) inhibited platelet aggregation in a dose-dependent manner. The IC50 of the most active substance, compound 2b, was around 60 microM against ADP and collagen as inducers. The inhibition of platelet aggregation caused by test compounds was dependent on the level of oxidation of the function at the 5-position, with the order of IC50 values being R-OH (2a, b, 5) < R-CHO (6, 7) < < R-COOH (8, 9). None of the tested compounds increased the intracellular levels of cAMP, indicating a lack of inhibitory activity on cAMP phosphodiesterase (PDE III) in intact cells. These results suggest that the group present at the 5 position of 6-aryl-5-substituted pyridazinones determines the platelet aggregation-inhibitory activity, and that a mechanism other than PDE inhibition is responsible for this effect.
- Published
- 1997
- Full Text
- View/download PDF
178. Clinical tolerance, parasitological efficacy and environmental effects of dehumidifiers in stable asthmatics sensitized to house dust mites.
- Author
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Chivato T, Montoro A, Martínez D, Gil P, Zubeldia J, De Barrio M, Baeza ML, Rubio M, and Laguna R
- Subjects
- Animals, Anti-Asthmatic Agents therapeutic use, Asthma drug therapy, Asthma immunology, Mites physiology, Severity of Illness Index, Temperature, Asthma prevention & control, Dust, Household Articles, Humidity, Mites immunology
- Abstract
Dehumidifiers (DH) are potentially effective appliances as coadjuvant therapy in the treatment of bronchial asthma caused by sensitization to house dust mites. The aims of this study were to analyze DH tolerance in asthmatic patients, to assess the parasitological effects and to analyze the environmental effects produced by the use of these appliances in the bedrooms of asthmatic patients sensitized to house dust mites. 10 stable asthmatic patients sensitized to house dust mites were studied. DH appliances (CD-300) were installed in their bedrooms. Each patient was given symptom scoring tables and a portable peak expiratory flow (P.E.F.) during a period of 5 months, 1 month before installing the DH and 4 months afterwards. To study the parasitological efficacy of the DHs, we analyzed dust samples from the bedrooms and determined the Der p I, Der f I and Der II allergens by means of a modified ELISA based on monoclonal antibodies. Dust samples were collected before installing the DHs and after they had been working for 2 and 4 months. Dry temperature and relative humidity measurements at three time intervals (7-9, 15-17 and 22-24 h) were carried out. The 1st measurement was done prior to installation of the DHs in the patients' bedrooms and the 2nd and 3rd were achieved 2 and 4 months respectively after the installation. Statistical analysis was done by comparison of paired means. No significant differences were detected in the patients' symptoms nor in the P.E.F. measurements in the course of the study. Decreases in the house dust mite allergens were observed in 4 bedrooms. A significant decrease in relative humidity in the bedrooms of mite asthma patients after use of dehumidifier appliances was observed (p < 0.01). Significant differences between the measurements of the bedrooms with and without DH were detected (p < 0.01). In summary, DHs were well tolerated by stable asthmatic patients, produced a significant decrease in the relative humidity level and showed some parasitological efficacy.
- Published
- 1997
179. Serum levels of eosinophil cationic protein and eosinophil protein x in pollen atopic patients with stable asthma and its relation with bronchial hyperresponsiveness.
- Author
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Chivato T, Martínez D, Blasco R, Melgarejo M, Gómez de Terreros FJ, and Laguna R
- Subjects
- Allergens, Eosinophil Granule Proteins, Eosinophil-Derived Neurotoxin, Humans, Leukocyte Count, Pollen, Asthma blood, Asthma physiopathology, Blood Proteins analysis, Bronchial Hyperreactivity physiopathology, Rhinitis, Allergic, Seasonal blood, Rhinitis, Allergic, Seasonal physiopathology, Ribonucleases
- Abstract
Eosinophils are important effector cells in allergic inflammation described in allergic rhinitis (AR) and allergic bronchial asthma (BA). During the pollen season serum levels of eosinophil cationic protein (ECP) and eosinophil X protein/eosinophil-derived neurotoxin (EPX/EDN) are increased in BA. The aim of the present study was to evaluate the serum levels of ECP and EPC in pollen atopic patients with AR and BA during the winter. 92 patients were studied. They were divided into three groups: I 29 patients with AR, II 51 patients with BA and III 12 healthy subjects. Allergic rhinitis and bronchial asthma were diagnosed by routine clinical tests: clinical history, skin tests, total IgE and specific IgE. In addition ECP and EPX were determined in serum. All patients were asymptomatic, stable and without medical treatment. Methacholine challenge test (MCT) was performed in all patients. MCT were positive in 4 patients of group I and 45 patients of group II. ECP levels (ug/l) were: 21 (I), 24 (II) and 7 (III). EPX levels (ug/l) were 35 (I), 45 (II) and 21 (III). Statistical differences (p < 0.01) were observed both in ECP and EPX levels in patients with MCT positive in relation to patients with MCT negative, and in allergic patients (I and II) in comparison with the healthy subjects (III) (p < 0.01). ECP and EPX serum levels are increased in patients with a positive MCT in the winter, out of the pollen season, when patients are asymptomatic, stable and without treatment. This fact suggests that eosinophils play an important role in the pathogenesis of bronchial asthma.
- Published
- 1996
180. Anaphylaxis induced by ingestion of a pollen compound.
- Author
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Chivato T, Juan F, Montoro A, and Laguna R
- Subjects
- Adult, Humans, Male, Phytotherapy, Anaphylaxis etiology, Plants, Medicinal immunology, Pollen immunology
- Abstract
We report on the case of a 32-year-old atopic patient who showed a severe anaphylactic reaction due to the ingestion of a pollen compound prepared in an herbalist's. A few minutes after ingestion, generalized pruritus, difuse erythema, facial edema, cough, hoarseness and dysphonia appeared, and the emergency administration of subcutaneous epinephrine and intravenous methylprednisolone was necessary. Skin tests with a battery of inhalants and food allergens were performed. The patient only showed sensitization to Artemisia vulgaris, Taraxacum officinalis and Salix alba. Specific IgE levels were evaluated by FEIA-CAP giving a seric level of CAP class 3 to Artemisia vulgaris and class 2 to Taraxacum officinalis and Salix alba. Samples of the pollen compound were shown in the microscopical analysis to be 93% pollens and 6% fungi. In the qualitative study Taraxacum officinalis (15%), Artemisia vulgaris (5%) and Salix alba (15%) were the main elements identified. In summary, this case study describes a food-induced systemic reaction due to a pollen compound in an atopic patient with a history of allergic rhinitis. Pollinic patients must be informed on the risks that the consumption of these compounds might cause.
- Published
- 1996
181. Scintigraphic findings in a Brodie's abscess.
- Author
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Silva F, Laguna R, Acevedo M, Ruíz C, and Orduña E
- Subjects
- Child, Preschool, Female, Gallium Radioisotopes, Humans, Radionuclide Imaging, Technetium Tc 99m Medronate, Abscess diagnostic imaging, Femur Neck diagnostic imaging, Osteomyelitis diagnostic imaging
- Abstract
A 9-year-old girl had a 6-month history of left hip pain. Radiographs of the left hip showed a metaphyseal osteolytic lesion with sclerotic borders in the femoral neck. Tc-99m MDP bone imaging and a Ga-67 scan showed focal areas of increased activity in the left femoral neck. These areas of increased uptake corresponded to a lytic area on x-rays, which was due to a Brodie's abscess. The combination of Tc-99m MDP bone and Ga-67 imaging has been widely used in the confirmation of bone infection, increasing the accuracy in the diagnosis of osteomyelitis. However, nuclear scintigraphy has not been previously reported in the confirmation of a Brodie's abscess.
- Published
- 1995
- Full Text
- View/download PDF
182. [Cytologic and biochemical component in 203 bronchoalveolar lavages. Reference values].
- Author
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Alvarez-Sala R, Alvarez-Sala JL, Prados C, Callol L, Laguna R, Blasco R, Villamor J, and Gómez de Terreros FJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers analysis, Female, Humans, Male, Middle Aged, Reference Values, Respiratory Tract Diseases pathology, Therapeutic Irrigation standards, Bronchoalveolar Lavage Fluid chemistry, Bronchoalveolar Lavage Fluid cytology
- Abstract
The bronchoalveolar lavage (BAL) is considered a basic technique as a diagnostic aid in Pneumology. However, one of the main problems faced by the clinician is the lack of standardization of the technique. This has been resolved through the drafting of international standards. The other problem is the lack of what might be called a "reference" BAL. In order to establish a reference BAL, we analyzed 203 BAL divided in two groups: a control group and a pathologic group, make up by extrinsic asthma, intrinsic asthma, pulmonary infections, diffuse interstitial pneumopathies, bronchopulmonary tumors and chronic bronchitis. We have studied both the cytologic and the biochemical component of the BAL. Among the biochemical markers, we have considered; carcinoembrionary antigen (CEA), tissular polypeptidic antigen (TPA), neuronal specific enolase (NSE), ferritin (FER), calcitonin (CT), ACTH, histamin (HIS) and prostaglandin (PGE2). In order to establish the reference values, we have used the modified Baye's theorema. The BAL that we obtained was the following: volume 20 ml, cells 35 x 10(5) cells/ml, macrophages 77%, lymphocytes 22%, neutrophils 4%, eosinophils 2%, CEA 14 ng/mg, TPA 84 U/g PT, NSE 5 ng/mg PT, FER 42 ng/mg PT, CT 15 pg/mg PT, ACTH 51 pg/mg PT, HIS 1.22 ng/mg PT, PGE2 35 pg/mg PT.
- Published
- 1995
183. Tumour markers in broncho-alveolar lavage.
- Author
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Alvarez-Sala R, Blasco R, Callol L, Laguna R, Alvarez-Sala JL, and Gomez de Terreros FJ
- Subjects
- Adult, Aged, Female, Humans, Lung Diseases metabolism, Male, Middle Aged, Biomarkers, Tumor analysis, Bronchoalveolar Lavage Fluid analysis, Lung Neoplasms metabolism
- Published
- 1989
- Full Text
- View/download PDF
184. [Acute lymphocytic leukaemia with erythrophagocytic activity (author's transl)].
- Author
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Fernández MN, Barbolla L, Sanjuán I, Cabrera R, Zabala P, Regidor C, Coton C, Laguna R, Ortiz de Landazuri M, and Durántez A
- Subjects
- Adult, Antineoplastic Agents administration & dosage, B-Lymphocytes physiology, Drug Therapy, Combination, Erythrocytes, Female, Humans, Leukemia, Lymphoid drug therapy, Phagocytosis, Leukemia, Lymphoid blood
- Published
- 1981
185. [Diagnostic importance of the mouse erythrocyte receptor in lymphoproliferative syndromes].
- Author
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Laguna R, Alvarez de Mon M, Casas J, Jordá J, and Durántez A
- Subjects
- Animals, B-Lymphocytes immunology, Humans, Lymphocytosis diagnosis, Mice, Phenotype, Receptors, Antigen, B-Cell analysis, Receptors, Antigen, B-Cell immunology, Receptors, Immunologic analysis, Sheep immunology, Erythrocytes immunology, Lymphoproliferative Disorders diagnosis, Receptors, Immunologic immunology
- Published
- 1987
186. Lymphokine induction of NK-like cytotoxicity in T cells from B-CLL.
- Author
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Alvarez de Mon M, Casas J, Laguna R, Toribio ML, de Landázuri MO, and Durántez A
- Subjects
- Aged, B-Lymphocytes, Humans, Interferon-gamma pharmacology, Middle Aged, Cytotoxicity, Immunologic drug effects, Interleukin-2 pharmacology, Killer Cells, Natural immunology, Leukemia, Lymphoid immunology, T-Lymphocytes immunology
- Abstract
T cells from patients with B cell chronic lymphocytic leukemia (B-CLL) exhibit defective natural killer (NK) activity. In this study, we have analyzed the cytotoxic-inducer effects of gamma interferon (gamma-IFN) and supernatants containing interleukin 2 (IL 2 sup). T cells from patients with B-CLL were incubated with gamma-IFN or IL 2 sup. gamma-IFN did not modulate the very low or undetectable levels of NK activity present in the T cell population. However, the IL 2 sup induced a potent cellular cytotoxicity against NK-sensitive and NK-resistant tumoral target cells. This cytotoxic inducer effect (a) was present in lectin-free IL 2 sup and in a 15,000- to 20,000-dalton molecular weight fraction obtained by gel filtration chromatography of this supernatant; (b) was directed against NK-sensitive and NK-resistant target cells; (c) was not correlated with the basal levels of NK activity; and (d) was not associated with a development or augmentation of the proportion of lymphocytes with classic NK cell phenotype. Taken together, these results demonstrate that unstimulated T cells from B-CLL patients, incubated briefly (18 hours) with IL 2 sup but not gamma-IFN, have strong NK-like cytotoxicity, despite the lack of classic NK activity.
- Published
- 1986
187. [Behavior of leukocyte chemotaxis in various clinico-immunological situations].
- Author
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Suárez Saro JM, Laguna Martínez R, Callol Sánchez L, Caro de Miguel C, and Gómez de Terrenos Sánchez FJ
- Subjects
- Adult, Anemia, Sickle Cell immunology, Bacterial Infections immunology, Diabetes Mellitus immunology, Female, Humans, Immunity, Cellular, Immunologic Deficiency Syndromes immunology, Immunologic Techniques, Kidney Failure, Chronic immunology, Liver Cirrhosis immunology, Male, Middle Aged, Neoplasms immunology, Neutrophils immunology, Pneumonia immunology, Prospective Studies, Chemotaxis, Leukocyte, Skin Window Technique, Tuberculosis, Pulmonary immunology
- Abstract
Chemotaxis is a property common to all free cells or unicellular microorganisms. It is not a simple spontaneous cellular migration but one which is directed towards the source or nucleus, producer of the chemotactic substance. One of the first phenomenon which is established as a defense mechanism of the organism is the attraction of polymorphonuclears. In 1955 Rebuck and Crowley described a method, "skin window" for the study of in vivo leukocyte chemotaxis. The aim of this work was to go deeper into the study of this test and to establish its clinical use. Two hundred and seventy patients from both sexes were studied and divided into five groups: Group I - 60 healthy subjects as control. Group II - 60 patients with pathologic leukocyte response: 10 cirrhotics, 15 Hodgkin's disease, 15 chronic renal insufficiency, 2 drepanocytosis and 3 sarcoidosis. Group III - 60 patients with no theoretical alterations in the leukocyte chemotaxis: 22 bronchial asthma, 23 nonlymphoid neoplasm, 13 iritis and 2 histiocytosis X. Group IV - 40 active tuberculosis patients. Group V - 30 patients with bacterial pneumonia non-tuberculosis. The Rebuck test was carried out on all patients. As lymphocyte markers, E rosettes, superficial immunoglobulins and the lymphoblast transformation test against PHA were performed on all the groups of patients. As to the results obtained, the positive responses for Groups I, II, III, IV and V were 87%, 28%, 83.3%, 45% and 63.3%, respectively. These results were evaluated in relation to the Mantoux reaction. The modified Rebuck test is useful for leukocyte chemotactic study. This was found to be altered in 13% of the healthy population.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1985
188. Clinical signification of natural killer activity in B-cell chronic lymphocytic leukemia.
- Author
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Alvarez-Mon M, Casas J, Laguna R, Jordá J, and Durantez A
- Subjects
- Animals, B-Lymphocytes, Blood Cells physiology, Erythrocytes immunology, Humans, Killer Cells, Natural immunology, Leukemia, Lymphoid pathology, Neoplasm Staging, Neuraminidase, Rosette Formation, Sheep blood, Killer Cells, Natural physiology, Leukemia, Lymphoid physiopathology
- Abstract
The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase-treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B-cell chronic lymphocytic leukemia (B-CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p less than 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p greater than 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B-CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p less than 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B-CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.
- Published
- 1987
- Full Text
- View/download PDF
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