Evolution of organ procurement and donor characteristics in Spain.
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Accidents, Traffic↗
Biomedical subjects
M Sanchez
Publications and source records attributed to M Sanchez.
On the road to perinatal case management.
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Humans↗
[Long-term follow-up of Parks posterior repair. An electromyographic, manometric and radiologic study of 31 patients].
This study was carried out to document the long-term results of postanal repair for idiopathic faecal incontinence. Thirty-one patients (mean age 65.6 years) were followed up for 2-7.5 years (median 4.2 years). Continence was improved in 16 (52%) patients, only 2 (6%) of whom regained normal continence. No significant change in resting and pressure, maximum squeeze pressure, pelvic descent or anorectal angle was seen postoperatively. The electromyographical signs, e.g. duration and amplitude of action potentials, average amplitude, and integrals of the curves did not change significantly after the operation. The mean right pudendal nerve terminal motor latency (PNTML) increased from 2.38 ms before to 2.59 ms after surgery (P > 0.05). No significant change in the continence and defaecation index was seen postoperatively.
Aged↗
Magnetic resonance imaging of paraganglioma of the cauda equina.
The authors describe atypical magnetic resonance imaging (MRI) findings for pathologically proven paraganglioma of the filum terminale in a 27-year-old man. MRI showed an intradural tumour, which enhanced after administration of gadolinium and which showed evidence of cystic areas. Hemosiderin rings and vessels were not observed.
Adult↗
A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB modulates B-cell receptor signalling.
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Amino Acid Sequence↗
Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels.
Tremorgenic indole alkaloids produce neurological disorders (e.g., staggers syndromes) in ruminants. The mode of action of these fungal mycotoxins is not understood but may be related to their known effects on neurotransmitter release. To determine whether these effects could be due to inhibition of K+ channels, the interaction of various indole diterpenes with high-conductance Ca(2+)-activated K+ (maxi-K) channels was examined. Paspalitrem A, paspalitrem C, aflatrem, penitrem A, and paspalinine inhibit binding of [125I]charybdotoxin (ChTX) to maxi-K channels in bovine aortic smooth muscle sarcolemmal membranes. In contrast, three structurally related compounds, paxilline, verruculogen, and paspalicine, enhanced toxin binding. As predicted from the binding studies, covalent incorporation of [125I]ChTX into the 31-kDa subunit of the maxi-K channel was blocked by compounds that inhibit [125I]ChTX binding and enhanced by compounds that stimulate [125I]ChTX binding. Modulation of [125I]ChTX binding was due to allosteric mechanisms. Despite their different effects on binding of [125I]ChTX to maxi-K channels, all compounds potently inhibited maxi-K channels in electrophysiological experiments. Other types of voltage-dependent or Ca(2+)-activated K+ channels examined were not affected. Chemical modifications of paxilline indicate a defined structure-activity relationship for channel inhibition. Paspalicine, a deshydroxy analog of paspalinine lacking tremorgenic activity, also potently blocked maxi-K channels. Taken together, these data suggest that indole diterpenes are the most potent nonpeptidyl inhibitors of maxi-K channels identified to date. Some of their pharmacological properties could be explained by inhibition of maxi-K channels, although tremorgenicity may be unrelated to channel block.
Allosteric Regulation↗
A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB modulates B-cell receptor signalling.
The Fc receptor on B lymphocytes, Fc gamma RIIB (beta 1 isoform), helps to modulate B-cell activation triggered by the surface immunoglobulin complex. Crosslinking of membrane immunoglobulin by antigen or anti-Ig F(ab')2 antibody induces a transient increase in cytosolic free Ca2+, a rise in inositol-3-phosphate, activation of protein kinase C, and enhanced protein tyrosine phosphorylation. Crosslinking Fc gamma RIIB with the surface immunoglobulin complex confers a dominant signal that prevents or aborts lymphocyte activation triggered through the ARH-1 motifs of the signal transduction subunits Ig-alpha and Ig-beta. Here we show that Fc gamma RIIB modulates membrane immunoglobulin-induced Ca2+ mobilization by inhibiting Ca2+ influx, without changing the pattern of tyrosine phosphorylation. A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB is both necessary and sufficient for this effect. Tyrosine at residue 309 in this motif is phosphorylated upon co-crosslinking with surface immunoglobulin; mutation of this residue aborts the inhibitory effect of Fc gamma RIIB. This inhibition is directly coupled to signalling mediated through Ig-alpha and Ig-beta as evidenced by chimaeric IgM/alpha and IgM/beta molecules. The 13-residue motif in Fc gamma RIIB controls lymphocyte activation by inhibiting a Ca2+ signalling pathway triggered through ARH-1 motifs as a result of recruitment of novel SH2-containing proteins that interact with this Fc gamma RIIB cytoplasmic motif.
Amino Acid Sequence↗
Yeast exo-beta-glucanases can be used as efficient and readily detectable reporter genes in Saccharomyces cerevisiae.
Yeast exo-1,3-beta-glucanases are secretable proteins whose function is basically trophic and may also be involved in cell wall glucan hydrolytic processes. Since fluorescein di(beta-D-glucopyranoside) is a fluorogenic substrate detectable and quantifiable by flow cytometry, it was used for testing the ability of the EXG1 gene product of Saccharomyces cerevisiae and its homologous gene in Candida albicans to function as reporter genes. These open reading frames were coupled to different promoters in multicopy plasmids, and exoglucanase activity quantified at flow cytometry. Exoglucanases were found to be useful tools for the study of promoter regions in S. cerevisiae. This technique has the advantage over other reporter gene systems--such as beta-galactosidase fusions--that it does not require permeabilization of yeast cells and therefore it allows the recovery of viable cells--by sorting--after flow cytometry analysis.
Flow Cytometry↗
Efficacy of flecainide in patients with supraventricular arrhythmias and respiratory insufficiency.
OBJECTIVE: Evaluation of efficacy of intravenous flecainide to revert supraventricular arrhythmias to sinus rhythm in patients with respiratory insufficiency. DESIGN: Comparative randomized prospective trial. SETTING: ICU in a University Hospital. PATIENTS: 30 patients with acute respiratory insufficiency or acute exacerbation of chronic respiratory insufficiency and supraventricular arrhythmias. Intravenous flecainide was administered to 15 patients (Group A) (2 mg/kg for 10 min and continuous perfusion of 1.5 mg/kg for 1 h). Intravenous verapamil was administered to 15 patients (Group B) (0.15 mg/kg for 5 min and continuous perfusion of 0.005 mg/kg/min for 1 h). MEASUREMENTS AND RESULTS: The categories of patients' arrhythmias were: Group A-atrial fibrillation (AF) in 5 cases, atrial flutter (AFl) in 2, multifocal atrial tachycardia (MAT) in 4 and other supraventricular tachycardia (SVT) in 4. Group B-AF in 6 cases, AFL in 2, MAT in 2 and SVT in 5 cases. Flecainide reverted arrhythmias to sinus rhythm in 12 out of 15 cases (80%); of these 12, 11 reverted with the initial bolus. Verapamil reverted 5 out of 12 cases (33.3%, p < 0.01). No significant secondary adverse effects were detected. CONCLUSION: Intravenous flecainide is an effective antiarrhythmic drug to treat acute supraventricular arrhythmias in patients with respiratory insufficiency.
Acute Disease↗
[Results of anterior levator and externus-plasty in idiopathic anorectal incontinence. A prospective manometric, electromyography and radiology study].
A prospective clinical manometric and radiological study has been performed, before and after anterior levatorplasty and sphincter plication on 18 patients (mean age 61.6 years) with neurogenic faecal incontinence. Continence was improved on 15 (83%) patients, 13 (72%) patients were continent to solid and liquid stool, 3 (17%) of whom regained normal continence only, at a minimum of 6 months follow-up (phi 21.5 months). Postoperatively there was a significant increase in the resting anal pressure (p = 0.05) an maximum voluntary contraction pressure (p = 0.001). No significant change in sphincter length, duration of the action potentials, pudendal nerve terminal motor latency (PNTML), pelvic descent or anorectal angle was seen postoperatively. The incontinence and defaecation-score showed postoperatively a significant difference concerning soiling, time from urgency to defaecation, and discrimination between flatus and stool.
Aged↗
Incontinentia pigmenti: MR demonstration of brain changes.
PURPOSE: To describe the MR findings in eight girls and women with incontinentia pigmenti, from two families. Four had skin lesions and neurologic disease, and four had only skin lesions. METHODS: Eight patients had physical examination, family history, electroencephalogram and MR examination of the brain. MR was repeated in the two cases with more severe changes several years after the first study. RESULTS: MR revealed brain changes only in the four patients who had neurologic disease associated with the cutaneous lesions of incontinentia pigmenti. Abnormalities were located in the cerebral hemisphere contralateral to the most affected side of the body. In two cases, the MR changes were subjacent to the scalp areas where the most severe cutaneous lesions were located in the neonatal period. Hypoplasia of the corpus callosum, probably secondary to atrophy of one or both cerebral hemispheres, and abnormal signal and atrophy of the lateral regions of one of the cerebellar hemispheres also were found in all four cases. Although the changes were seen in both the T1- and T2-weighted images, they were most evident in the latter. The four patients in the fourth stage who had only cutaneous lesions without neurologic problems did not reveal any MR abnormalities. CONCLUSIONS: This study demonstrates MR signal changes and focal atrophy of the cerebrum, cerebellum, and corpus callosum in patients with incontinentia pigmenti and neurologic disorders. The MR images appear normal in patients with incontinentia pigmenti who have no neurologic abnormalities.
Adolescent↗
Phenylalanine and tyrosine kinetics in critically ill children with sepsis.
To better understand the impact of severe illness on the amino acid economy and nutritional needs of pediatric patients, we studied plasma phenylalanine and tyrosine kinetics in eleven critically ill patients (six full-term newborns and five young infants). Within 48 h of the diagnosis of sepsis they were given primed constant i.v. infusions of L-[1-13C]phenylalanine and L-[3,3,2H2]tyrosine for 4 h. Routine nutritional support continued during this period by parenteral administration of dextrose, lipid emulsion, and an amino acid mixture low in tyrosine. Phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation did not differ significantly between the two age groups, and so the data were combined for evaluation. For the entire group, values (mumol.kg-1.h-1; mean +/- SD) for phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation were 132 +/- 24, 66 +/- 16, and 29 +/- 12, respectively. Plasma phenylalanine to tyrosine concentration ratio was 1.67 +/- 0.6. From a comparison of the rate of phenylalanine hydroxylation with measured phenylalanine intakes, it was concluded that their routine, clinical nutritional support was inadequate to achieve body phenylalanine balance. In comparison with published data, the relative rate of phenylalanine hydroxylation appears to be high. We speculate that tyrosine is a conditionally indispensable amino acid under these conditions; it would be desirable to establish the intake levels and ratio of phenylalanine to tyrosine that effectively support aromatic amino acid balance in these critically ill patients.
Bacterial Infections↗
Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.
A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses.
Administration, Cutaneous↗
Alpha 2(I) collagen gene expression is up-regulated in quail chondrocytes pretreated with retinoic acid.
alpha 2(I) collagen gene expression is induced in quail embryo chondrocytes pretreated with retinoic acid (RA). The initial appearance of alpha 2(I) mRNA occurs around day 3 of culture in RA-free medium and rapidly progresses over the next 4 days. In transient transfection assays, expression of COL1A2-CAT, a chimeric gene bearing 3500 bp upstream the bone/tendon transcription start site from the human alpha 2(I) gene fused to the CAT gene, is stimulated severalfold in RA-treated chondrocytes. In contrast, enzyme activity is very low in untreated chondrocytes, suggesting that the sequences required for RA-induced transcription of the alpha 2(I) gene are present in this plasmid. Analysis of alpha 2(I) promoter sequences performed with deletion mutants gives overlapping results in collagen type I-producing fibroblasts and chondrocytes withdrawn from RA treatment. These experiments suggest that RA-induced transcription of the alpha 2(I) collagen gene in chondrocytes is regulated by the binding of transcription factors to the same regulatory sequences that control transcription in fibroblasts.
Animals↗
Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.
Immunoglobulin (Ig) antigen receptors are composed of a noncovalently-associated complex of Ig and two other proteins, Ig alpha and Ig beta. The cytoplasmic domain of both of these Ig associated proteins contains a consensus sequence that is shared with the signaling proteins of the T cell and Fc receptor. To test the idea that Ig alpha-Ig beta heterodimers are the signaling components of the Ig receptor, we have studied Ig mutations that interfere with signal transduction. We find that specific mutations in the transmembrane domain of Ig that inactivate Ca2+ and phosphorylation responses also uncouple IgM from Ig alpha-Ig beta. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Ig alpha with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig beta to the inactive Ig reconstitutes only Ca2+ responses. Thus, Ig alpha and Ig beta are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that Ig alpha and Ig beta can activate different signaling pathways.
Amino Acid Sequence↗
Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets.
The fluxes of arginine and citrulline through plasma and the rate of conversion of labeled citrulline to arginine were estimated in two pilot studies (with a total of six adult subjects) and in a dietary study with five healthy young men. These latter subjects received an L-amino acid-based diet that was arginine-rich or arginine-free each for 6 days prior to conduct, on day 7, of an 8-hr (first 3 hr, fast; final 5 hr, fed) primed continuous intravenous infusion protocol using L-[guanidino-13C]arginine, L-[5,5-2H2]citrulline, and L-[5,5,5-2H3]leucine, as tracers. A pilot study indicated that citrulline flux was about 20% higher (P < 0.05) when determined with [ureido-13C]citrulline compared with [2H2]citrulline, indicating recycling of the latter tracer. Mean citrulline fluxes were about 8-11 mumol.kg-1.hr-1 for the various metabolic/diet groups and did not differ significantly between fast and fed states or arginine-rich and arginine-free periods. Arginine fluxes (mean +/- SD) were 60.2 +/- 5.4 and 73.3 +/- 13.9 mumol.kg-1.hr-1 for fast and fed states during the arginine-rich period, respectively, and were significantly lowered (P < 0.05), by 20-40%, during the arginine-free period, especially for the fed state, where this was due largely to reduced entry of dietary arginine into plasma. The conversion of plasma citrulline to arginine approximated 5.5 mumol.kg-1.hr-1 for the various groups and also was unaffected by arginine intake. Thus, endogenous arginine synthesis is not markedly responsive to acute alterations in arginine intake in healthy adults. We propose that arginine homeostasis is achieved largely via modulating arginine intake and/or the net rate of arginine degradation.
Adult↗
The proximal region of the MBP gene promoter is sufficient to induce oligodendroglial-specific expression in transgenic mice.
To characterize regulatory DNA sequences involved in oligodendroglial expression of myelin basic protein (MBP), transgenic mice carrying a 256 bp fragment of the mouse MBP promoter fused to an Escherichia coli lacZ gene were generated. Of four transgenic families, two (lines 2 and 4) expressed beta-galactosidase activity in the nervous system but not in most other tissues. Histochemical and immunohistochemical analysis of adult brain from these two lines showed oligodendroglial-specific expression of the transgene. In line 2, only a small proportion of oligodendrocytes expressed the transgene, and in labelled cells the product of the enzymatic reaction with beta-galactosidase was confined to a small round vesicle in the vicinity of the nucleus. In contrast, in tissue sections from line 4 adult brain and spinal cord beta-galactosidase activity was much more intense and at least 80-90% of oligodendrocytes expressed the transgene. Detection of the MBP-lacZ transcript by in situ hybridization showed that the transgene mRNA was confined to the oligodendrocyte cell body. These results suggest that cis-acting regulatory elements, specifying oligodendrocytes identity, are located within 256 bp upstream from the MBP gene.
Aging↗
Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protein transferase.
Chaetomellic acids A and B, isolated from Chaetomella acutiseta, are specific inhibitors of farnesyl-protein transferase that do not inhibit geranylgeranyl transferase type 1 or squalene synthase. Chaetomellic acids A and B are reversible inhibitors, resemble farnesyl diphosphate and probably inhibit FPTase by substituting for farnesyl diphosphate. Chaetomellic acid production appears to be widespread within the genus Chaetomella.
Alkyl and Aryl Transferases↗