RESUMEN
The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies.
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Psiquiatría/historia , Esquizofrenia/terapia , Psicología del Esquizofrénico , Inglaterra , Francia , Alemania , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
BACKGROUND: Remodelling of the asthmatic airway includes increased deposition of proteoglycan (PG) molecules. One of the stimuli driving airway remodelling may be excessive mechanical stimulation. OBJECTIVE: We hypothesized that fibroblasts from asthmatic patients would respond to excessive mechanical strain with up-regulation of message for PGs. METHODS: We obtained fibroblasts from asthmatic patients (AF) and normal volunteers (NF) using endobronchial biopsy. Cells were maintained in culture until the fifth passage and then grown on a flexible collagen-coated membrane. Using the Flexercell device, cells were then subjected to cyclic stretch at 30% amplitude at 1 Hz for 24 h. Control cells were unstrained. Total RNA was extracted from the cell layer and quantitative RT-PCR performed for decorin, lumican and versican mRNA. RESULTS: In unstrained cells, the expression of decorin mRNA was greater in AF than NF. With strain, NF showed increased expression of versican mRNA and AF showed increased expression of versican and decorin mRNA. The relative increase in versican mRNA expression with strain was greater in AF than NF. CONCLUSIONS: These data support the hypothesis that proteoglycan message is increased in asthmatic fibroblasts subject to mechanical strain. This finding has implications for the mechanisms governing airway wall remodelling in asthma.
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Asma/metabolismo , Fibroblastos/metabolismo , Proteoglicanos/metabolismo , Adulto , Análisis de Varianza , Asma/patología , Bronquios/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estrés MecánicoRESUMEN
In order to examine the genetic substrate of the dopamine hypothesis in restless legs syndrome, we analyzed eight genes coding for receptors and enzymes related to dopaminergic transmission, using a population of 92 patients with restless legs syndrome and 182 controls matched for ethnic background. No significant differences were found in the genotypic or allelic distributions between groups. Furthermore, no effect of the loci examined was observed with stratification using clinical parameters such as age at onset or periodic leg movements during sleep index.
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Dopamina/genética , Síndrome de las Piernas Inquietas/genética , Síndrome de las Piernas Inquietas/metabolismo , Transmisión Sináptica/genética , Adulto , Anciano , Anciano de 80 o más Años , Canadá , Estudios de Casos y Controles , Dopamina/metabolismo , Dopamina beta-Hidroxilasa/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Tirosina 3-Monooxigenasa/genéticaRESUMEN
Recently, we have found an association between bipolar disorder patients who are excellent responders to lithium prophylaxis and a polymorphic marker located in the first intron of the phospholipase C-gamma1 gene (PLC-gamma1) [Turecki et al., 1998: Mol Psychiatry 3:534-538]. As this variant is not known to be functional, we searched for other markers within the coding region, using single-strand conformational polymorphism (SSCP) analysis. We have identified three polymorphic sites localized in three different exons of the PLC-gamma1 gene (exons 9, 26, 31). Variation studies of these potentially functional sites in a group of 133 bipolar patients with an excellent response to lithium prophylaxis and a comparison group of 99 healthy controls showed no difference in genotype distributions for exon 9 (chi-square = 1.41, df = 2, P = 0.49), exon 26 (chi-square = 2.26, df = 2, P = 0.13), or exon 31 (chi-square = 1.41, df = 2, P = 0.49). Similar results were observed for allele distributions. These results suggest that our previous findings were not the result of linkage disequilibrium with these variants.
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Trastorno Bipolar/genética , Isoenzimas/genética , Litio/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Fosfolipasas de Tipo C/genética , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/etiología , Estudios de Casos y Controles , Exones , Genotipo , Humanos , Sistemas de Lectura Abierta , Fosfolipasa C gamma , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Peptide-N4-(N-acetyl-beta-d-glucosaminyl asparagine amidase) from Aspergillus tubigensis (PNGase At) was expressed in baculovirus-infected insect cells. The recombinant PNGase At was secreted and purified to homogeneity with a yield of 9.5 mg per liter of infected cell medium. Recombinant PNGase At migrated upon SDS-PAGE as a single-chain protein with a molecular mass of 78 kDa. This contrasts with the native Aspergillus enzyme which is "nicked" and migrates as two subunits each with a molecular weight about 43 kDa. Quantitation of total sugar by phenol-sulfuric acid suggests that the enzyme expressed in baculovirus-infected insect cells was substituted with 8-10 chains of carbohydrate of which 75% was released by Endoglycosidase F1. ESI-MS analysis of the oligosaccharides released from the recombinant PNGase At revealed similarity in the number of glycosylated residues but a significant difference in their composition, when compared to the carbohydrates of the native PNGase At. Despite differences in the primary structure and in the composition of glycan residues, the recombinant enzyme had the same specific activity as the native enzyme.
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Amidohidrolasas/química , Aspergillus/enzimología , Proteínas Recombinantes/química , Animales , Baculoviridae/genética , Células Cultivadas , Glicoproteínas/química , Proteínas de Insectos/química , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa/metabolismo , Espectrometría de Masas , Oligosacáridos/química , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Spodoptera/genética , Especificidad por SustratoRESUMEN
A new glycoamidase, peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase (PNGase) At, was discovered in the eukaryote Aspergillus tubigensis. The enzyme was purified to homogeneity, and the DNA sequence was determined by cloning in Escherichia coli. Over 80% of the deduced amino acid sequence was verified independently by Edman analysis and/or electrospray ionization-mass spectrometry of protease fragments of native PNGase At. This glycoamidase contains 12 potential asparagine-linked glycosylation sites, of which at least 9 sites are occupied with typical high mannose oligosaccharides. PNGase At consists of two non-identical glycosylated subunits that are derived from a single polypeptide gene precursor. Evidence is presented suggesting that autocatalysis is involved in subunit formation. PNGase At is an important new tool for analysis of asparagine-linked glycans; it can hydrolyze a broad range of glycopeptides, including those with core-linked alpha1-->6 or alpha1-->3 fucose, under conditions not favorable with existing glycoamidases.
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Aspergillus/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Cromatografía Líquida de Alta Presión , Clonación Molecular , ADN Complementario , Datos de Secuencia Molecular , Mapeo Peptídico , Polisacáridos/químicaRESUMEN
A study of dental malpractice claims closed during the 1970s was conducted using closed claim data available as a byproduct of a survey conducted by the Secretary's Commission on Medical Malpractice, U.S. Department of Health, Education, and Welfare. The intent of the authors of this study is to establish a baseline that can be used for future comparisons of dental malpractice. Far fewer cases of dental malpractice were found than expected, and specialists such as oral surgeons were at higher risk than general practitioners. One-half of the claims resulted in no payment to the plaintiff. Trial verdicts were reached in just over 7 percent of the cases, and 93 percent of the verdicts were in favor of the defendant. The amount of damages paid to claimants for dental cases was approximately one-third that paid on claims involving physicians or medical specialists. The median award to the plaintiff for dental malpractice was $750. Ninety-five percent of the awards made were under $5,000.