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1.
Gesundheitswesen ; 79(4): e39-e49, 2017 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-27097312

RESUMEN

Background and Objectives: Exposure to recreational noise is becoming increasingly important due to a change in leisure behavior amongst children and adolescents. The aim of this pilot study was to assess exposure of 6th grade pupils to recreational noise from portable listening devices (PLD). Furthermore, preventive measures to reduce recreational noise exposure should be identified. Methods: In "Ohrkan Kids", 38 Bavarian pupils aged 11 to 14 were interviewed regarding their music listening behavior using a standardized questionnaire. In addition, measurements of commonly used volume settings on the children's portable listening devices were carried out. Furthermore, the German Social Accident Insurance (DGUV), health insurance companies as well as health and education ministries of the German federal states were surveyed regarding their activities in the prevention of recreational noise exposure. Results: Based on the questionnaire data for weekly usage, 10 out of 31 children (32.3%) exceeded the upper exposure value of 85 dB recommended by labor protection law. Taking actually measured values, 9 out of 31 children (29%) exceeded this level. The DGUV and some federal states carry out specific projects for the prevention of recreational noise exposure. Conclusion: The large number of children with hazardous music consumption indicates that measures for the prevention of noise-induced hearing loss are already required for 11 to 14 year olds. To maximize the number of children addressed, age-appropriate and target-group-specific preventive measures are needed. As there are only few studies which examined the effectiveness of awareness campaigns for the prevention of recreational noise, any future prevention projects should be evaluated with an increased focus on estimating their effectiveness.


Asunto(s)
Exposición a Riesgos Ambientales/prevención & control , Exposición a Riesgos Ambientales/estadística & datos numéricos , Pérdida Auditiva/epidemiología , Pérdida Auditiva/prevención & control , Ruido/efectos adversos , Recreación , Estudiantes/estadística & datos numéricos , Adolescente , Niño , Exposición a Riesgos Ambientales/análisis , Femenino , Alemania/epidemiología , Humanos , Masculino , Música , Proyectos Piloto , Prevalencia , Factores de Riesgo
2.
Pathologe ; 38(2): 98-104, 2017 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-28188377

RESUMEN

INTRODUCTION: Neuroendocrine Neoplasms are classified according to the new WHO classification in (1.) well differentiated neuroendocrine tumors G1 (NET G1, Ki67 ≤ 2 or mitosis count <2) and (2.) well differentiated neuroendocrine tumors G2 (NET G2, Ki67 3-20 or mitosis count 2-20) and (3.) poorly differentiated neuroendocrine carcinomas G3 (NEC G3, Ki67 > 20 or mitosis count >20). MATERIAL AND METHODS: In this study 310 NENs of the Ludwig-Maximilians-University in Munich were reevaluated according to the new WHO classification. RESULTS: 7% of the analyzed NENs were presented as neoplasias of the stomach. In NENs of the stomach three distinct subtypes are recognized: (1) type 1 associated with autoimmune chronic atrophic gastritis (2) type 2, associated with multiple endocrine neoplasia (MEN1) and Zollinger-Ellison Syndrom; and (3) type 3, sporadic tumors. DISCUSSION: Precursor lesions (i. e. hyperplasia of the ECL cells) are found in patients with hypergastrinaemia (type 1 and 2). This article should provide insights into the diagnosis of NENs of the stomach with emphasis on the new international standard.


Asunto(s)
Tumores Neuroendocrinos/clasificación , Neoplasias Gástricas/clasificación , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Diferenciación Celular , Gastritis/complicaciones , Gastritis/diagnóstico , Humanos , Hiperplasia/patología , Antígeno Ki-67/genética , Mitosis , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Organización Mundial de la Salud , Síndrome de Zollinger-Ellison/complicaciones , Síndrome de Zollinger-Ellison/diagnóstico
3.
Klin Monbl Augenheilkd ; 229(3): 241-5, 2012 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-22105538

RESUMEN

BACKGROUND, MATERIAL AND METHODS: 1. An evaluation of medical findings and photodocumentation of 6 patients with pseudoexfoliation (PEX) material on the anterior surface of posterior chamber intraocular lenses was undertaken. Molecular genetic analysis of mutations in LOX-L1 was performed in order to confirm the association with pseudoexfoliation syndrome or glaucoma. Age of patients, the maximal intraocular pressure and perimetry with Octopus and Goldmann perimeters were documented as well as the time between implantation of the posterior chamber lens and diagnosis of pseudoexfoliation material on the anterior surface of posterior chamber lens. 2. Consecutive examinations of 35 patients with pseudoexfoliation syndrome or -glaucoma and pseudophakia were made to evaluate the frequency of patients with pseudoexfoliation material on the anterior surface of posterior chamber lenses. RESULTS: 1. The characteristic formation of stripe-shaped peripheral pseudoexfoliation material is seen in all examined patients on the anterior surface of posterior chamber lenses, but there is no central homogeneous round zone of pseudoexfoliation material in all patients. 2. the mean observation time of patients with pseudophakia and pseudoexfoliation syndrome or glaucoma is 4.4 ± 3.9 years. 5.7 % of the patients show pseudoexfoliation material in the periphery of posterior chamber lenses. The mean time between implantation of the intraocular lens and diagnosis of pseudoexfoliation material on the lenses is 3 years. CONCLUSIONS: The lack of a central homogeneous round zone of pseudoexfoliation material deposits on the anterior surface of posterior chamber lenses seems to be characteristic. The change in topography of PEX material on intraocular lenses is described here for the first time. A knowledge of this change in the topography of pseudoexfoliation material in pseudophakia is important for glaucoma screening, because pseudoexfoliation deposits can only be detected in mydriasis due to the peripheral location on the intraocular lens. Due to the old age of patients at the onset of pseudoexfoliation deposits, a pseudoexfoliation syndrome frequently is likely to develop after cataract surgery in many patients.


Asunto(s)
Síndrome de Exfoliación/complicaciones , Síndrome de Exfoliación/patología , Tamizaje Masivo/métodos , Oftalmoscopía/métodos , Seudofaquia/complicaciones , Seudofaquia/diagnóstico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
Am J Med Genet B Neuropsychiatr Genet ; 159B(8): 908-27, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22976950

RESUMEN

An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain.


Asunto(s)
Conducta Animal , Modelos Animales de Enfermedad , Conducta Materna , Polimorfismo de Nucleótido Simple , Trastornos Psicóticos/genética , Trastornos Puerperales/genética , Animales , Trastorno Bipolar/genética , Mapeo Cromosómico , Proteínas de Unión al ADN/genética , Depresión Posparto/genética , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Haplotipos , Humanos , Recién Nacido , Desequilibrio de Ligamiento , Sitios de Carácter Cuantitativo/genética , Proteínas de Unión al ARN/genética , Porcinos
5.
Mol Psychiatry ; 14(10): 959-67, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19255582

RESUMEN

Adult hippocampal neurogenesis is a unique example of structural plasticity, the functional role of which has been a matter of intense debate. New transgenic models have recently shown that neurogenesis participates in hippocampus-mediated learning. Here, we show that transgenic animals, in which adult hippocampal neurogenesis has been specifically impaired, exhibit a striking increase in anxiety-related behaviors. Our results indicate that neurogenesis plays an important role in the regulation of affective states and could be the target of new treatments for anxiety disorders.


Asunto(s)
Ansiedad/fisiopatología , Hipocampo/fisiología , Neurogénesis/fisiología , Animales , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Recuento de Células , Clordiazepóxido/farmacología , Depresión/fisiopatología , Doxiciclina/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neurogénesis/efectos de los fármacos , Neurogénesis/genética , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
6.
Klin Monbl Augenheilkd ; 227(11): 887-91, 2010 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-21077021

RESUMEN

PURPOSE: The success of trabeculectomy in glaucoma not sufficiently controlled by maximal medical therapy substantially depends on postoperative scarring of the filtering bleb. This process of scarring can be inhibited by antimetabolites like mitomycin C (MMC) and 5-fluorouracil (5-FU). The aim of this study is the evaluation of incidence and long-term outcome of corneal surface defects and intraocular pressure following MMC- or 5FU-trabeculectomy using different doses of postoperative 5FU. METHODS: A retrospective, non-randomised comparative study of 381 patients undergoing trabeculectomy with intraoperative application of either 5FU (group A, n = 169) or MMC (group B, n = 212) was performed. Based on the Wuerzburg bleb classification score (WBCS) for postoperative wound healing evaluation, 30 of these operations of group A (group B: n = 26) did not receive 5 FU postoperatively (controls), 67 (93) received up to 7 postoperative injections of 5 mg 5 FU (normal dosage group), and 72 (93) received more than 7 injections (high dosage group). Surface epithelial defects were routinely assessed by slit-lamp microscopy and fluorescein staining. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry. RESULTS: In the normal dosage group the mean total dose of 5 FU was 25.8 ± 9.1 mg in group A (group B: 28.4 ± 7.5 mg) and in the high dosage group 54.2 ± 10.9 mg 5 FU (51.7 ± 11.8 mg), respectively. Increased doses of postoperative 5 FU induced more frequent corneal erosions in both groups. Corneal erosions were seen in controls in 16.7 % (26.9 %), in the normal dosage group in 55.2 % (47.3 %) and in the high dosage group in 77.8 % (59.1 %) in group A and group B, respectively. The incidence of a corneal erosion between group A and group B did not differ significantly (p = 0.074). The mean reduction of intraocular pressure in mmHg did not show a significant difference 12 months after trabeculectomy between controls and postoperative 5-FU operations. CONCLUSION: In eyes with beginning scarring of the filtering bleb after trabeculectomy the subconjunctival injection of 5-FU allows a similar reduction of intraocular pressure as in eyes without scarring. Corneal epitheliopathy following trabeculectomy and postoperative 5 FU is dose-dependent with higher doses leading to a higher incidence of corneal erosions. As serious corneal long-term complications are rare, risk-benefit analysis justifies the application of 5-FU after filtrating glaucoma surgery.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Enfermedades de la Córnea/inducido químicamente , Epitelio Corneal/efectos de los fármacos , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Presión Intraocular/efectos de los fármacos , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Trabeculectomía/efectos adversos , Anciano , Terapia Combinada , Enfermedades de la Córnea/diagnóstico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intraoculares , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos
7.
Science ; 286(5449): 2498-500, 1999 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-10617463

RESUMEN

Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide.


Asunto(s)
Esclerosis Amiotrófica Lateral/enzimología , Apoptosis , Neuronas Motoras/citología , Óxido Nítrico/metabolismo , Superóxido Dismutasa/metabolismo , Zinc/metabolismo , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Animales , Factor Neurotrófico Derivado del Encéfalo/farmacología , Células Cultivadas , Quelantes/farmacología , Cobre/metabolismo , Fluoresceínas/metabolismo , Liposomas , Neuronas Motoras/metabolismo , Mutación , Nitratos/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , Oxidación-Reducción , Ratas , Superóxido Dismutasa/química , Superóxido Dismutasa/genética , Superóxido Dismutasa/toxicidad , Superóxidos/metabolismo
8.
Neuron ; 15(2): 259-71, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7646884

RESUMEN

The 104 kDa irreC-rst protein, a member of the immunoglobulin superfamily, mediates homophilic adhesion in cell cultures. In larval optic chiasms, the protein is found on recently formed axon bundles, not on older ones. In developing visual neuropils, it is present in all columnar domains of specific layers. The number of irreC-rst-positive neuropil stratifications increases until the midpupal stage. Immunoreactivity fades thereafter. The functional importance of the restricted expression pattern is demonstrated by the severe projection errors of axons in the first and second optic chiasms in loss of function mutants and in transformants that express the irreC-rst protein globally. Epigenesis of the phenotypes can be explained partially on the bases of homophilic irreC-rst interactions.


Asunto(s)
Axones/fisiología , Moléculas de Adhesión Celular Neuronal/fisiología , Proteínas de Drosophila , Drosophila melanogaster/crecimiento & desarrollo , Proteínas del Ojo , Regulación del Desarrollo de la Expresión Génica , Hormonas de Insectos/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuronas/fisiología , Quiasma Óptico/crecimiento & desarrollo , Lóbulo Óptico de Animales no Mamíferos/crecimiento & desarrollo , Vías Visuales/crecimiento & desarrollo , Animales , Animales Modificados Genéticamente , Adhesión Celular , Moléculas de Adhesión Celular Neuronal/análisis , Moléculas de Adhesión Celular Neuronal/biosíntesis , Moléculas de Adhesión Celular Neuronal/genética , Agregación Celular , Células Cultivadas , Drosophila melanogaster/genética , Genes de Insecto , Calor , Hormonas de Insectos/biosíntesis , Hormonas de Insectos/genética , Larva , Microscopía Confocal , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Quiasma Óptico/citología , Quiasma Óptico/metabolismo , Lóbulo Óptico de Animales no Mamíferos/citología , Lóbulo Óptico de Animales no Mamíferos/metabolismo , Pupa , Proteínas Recombinantes de Fusión/inmunología , Transfección
10.
Clin Res Cardiol ; 106(7): 493-500, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28180940

RESUMEN

BACKGROUND: Whereas in-stent restenosis (ISR) is widely discussed after coronary stenting procedures, this phenomenon is a considerable problem after interventional treatment of carotid artery stenosis as well. We sought to quantify ISR rate and to identify important respective risk factors in our cohort. METHODS: We retrospectively analyzed data of our carotid artery stenting database comprising 1165 angiographically successful interventional procedures during the last 19 years. Significant ISR was assessed by Doppler ultrasound and defined as a flow velocity exceeding 300 cm/s representing a lumen narrowing >70%. Examinations were performed the day after intervention, at follow-up visits 1, 6 and 12 months after index hospitalization and once a year afterwards. RESULTS: Thirty-nine patients (3.4%) developed a significant ISR > 70% during the follow-up period (median 19.6 months, IQR 5.1-49.6 months). In 13 of them, restenosis was caused by a mechanical collapse (stent crush) of the implanted stent. All patients with significant ISR were free of neurological events during follow-up and 31 patients underwent a stent-in-stent implantation. We found a shorter stent length, a narrower stent diameter, performance of post-dilatation as well as stent type to significantly influence development of ISR. CONCLUSION: ISR > 70% after carotid artery stenting is a rare finding also during long-term follow-up. Especially in patients treated with balloon-expandable stents, post-dilatation reduced ISR significantly. As ISR was rare and clinically benign, this technique seems to remain a good therapy option in patients with significant carotid artery stenosis.


Asunto(s)
Arterias Carótidas/cirugía , Estenosis Carotídea/cirugía , Oclusión de Injerto Vascular/cirugía , Stents/efectos adversos , Anciano , Angiografía , Austria/epidemiología , Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/diagnóstico , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/diagnóstico , Oclusión de Injerto Vascular/epidemiología , Humanos , Incidencia , Masculino , Falla de Prótesis , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Ultrasonografía Doppler
11.
Circ Res ; 85(10): 970-5, 1999 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-10559145

RESUMEN

Intimal cushions that project into the lumen of arteries are precursors of atherosclerotic plaque formation. The "carotid siphon, " although frequently affected by atherosclerosis, was never analyzed for the occurrence of neonatal intimal hyperplasia. This study provides a topographic and morphometric analysis of intimal cushions in the parasellar internal carotid artery (pICA) of the human infant. A total of 35 specimens were studied in detail, using both standard histological techniques and a new method of computer-aided 3D reconstruction. Intimal hyperplasia occurred at 3 characteristic locations of the pICA: (1) the convex side of the posterior knee (C5 cushion), (2) the bottom of the horizontal segment (C4 cushion), and (3) the concave side of the anterior knee (C3 cushion). The extension of the cushions and the degrees to which they occluded the vessel lumens were measured. The complex shape of the pICA required 3D computer models for exact topographical descriptions and precise measurements. Our results suggest that the occurrence and degree of intimal hyperplasia are related to shape changes of the pICA during postnatal development. We predict that individuals who retain the relatively straight course of the fetal pICA throughout their lives are less prone to develop atherosclerotic lesions at this portion of the carotid artery. A possible contribution of neonatal intimal cushions to the origin of sudden infant death syndrome is discussed.


Asunto(s)
Arterias Carótidas/patología , Túnica Íntima/patología , Arteriosclerosis/etiología , Femenino , Humanos , Hiperplasia , Procesamiento de Imagen Asistido por Computador , Lactante , Recién Nacido , Masculino , Arteria Oftálmica/patología , Silla Turca , Muerte Súbita del Lactante/etiología
12.
J Neurosci ; 19(17): 7548-56, 1999 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-10460261

RESUMEN

To investigate a possible involvement of synaptic machinery in Drosophila visual system development, we studied the effects of a loss of function of neuronal synaptobrevin, a protein required for synaptic vesicle release. Expression of tetanus toxin light chain (which cleaves neuronal synaptobrevin) and genetic mosaics were used to analyze neuropil pattern formation and levels of selected neural adhesion molecules in the optic lobe. We show that targeted toxin expression in the developing optic lobe results in disturbances of the columnar organization of visual neuropils and of photoreceptor terminal morphology. IrreC-rst immunoreactivity in neuropils is increased after widespread expression of toxin. In photoreceptors, targeted toxin expression results in increased Fasciclin II and chaoptin but not IrreC-rst immunoreactivity. Axonal pathfinding and programmed cell death are not affected. In genetic mosaics, patches of photoreceptors that lack neuronal synaptobrevin exhibit the same phenotypes observed after photoreceptor-specific toxin expression. Our results demonstrate the requirement of neuronal synaptobrevin for regulation of cell adhesion molecules and development of the fine structure of the optic lobe. A possible causal link to fine-tuning processes that may include synaptic plasticity in the development of the Drosophila CNS is discussed.


Asunto(s)
Axones/fisiología , Moléculas de Adhesión Celular/genética , Drosophila melanogaster/crecimiento & desarrollo , Proteínas de la Membrana/metabolismo , Lóbulo Óptico de Animales no Mamíferos/crecimiento & desarrollo , Células Fotorreceptoras de Invertebrados/crecimiento & desarrollo , Animales , Apoptosis , Drosophila melanogaster/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas Fluorescentes Verdes , Larva , Proteínas Luminiscentes/biosíntesis , Proteínas Luminiscentes/genética , Mosaicismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/fisiología , Pupa , Proteínas R-SNARE , Proteínas Recombinantes de Fusión/biosíntesis , Toxina Tetánica/biosíntesis , Toxina Tetánica/genética , Vías Visuales/crecimiento & desarrollo
13.
Neurobiol Aging ; 15(1): 103-11, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7909140

RESUMEN

The excitatory amino acids (EAAs) L-aspartate and L-glutamate constitute the major neurotransmitters in the mammalian brain. This study established the influence of aging and oxidative stress on the release and uptake of EAAs. The high affinity uptake of D-[3H]aspartate in synaptosomal fractions of the neostriatum, hippocampus, and neocortex was not significantly different in Fisher 344/Norwegian Brown hybrid rats aged 3, 12, 24, and 37 months. Similarly, the K(+)-evoked efflux of endogenous aspartate and glutamate from neocortical minislices was also unaffected by age. To examine the possibility that EAA nerve terminals become more vulnerable to oxidative stress with age, the influence of an inhibitor of the electron transport chain (sodium cyanide) on EAA uptake and release was determined. Although cyanide inhibited D-[3H]aspartate uptake and potentiated the potassium-evoked efflux of aspartate and glutamate in a Ca(2+)-independent fashion, neither of these changes were influenced by age. Thus, the functional integrity of EAA nerve terminals and their vulnerability to oxidative stress are both preserved in normal aging. The potency of cyanide to inhibit D-[3H]aspartate uptake did, however, display regional variability: hippocampus > neocortex > neostriatum (IC50 = 1.2 +/- 0.2 mM, 1.9 +/- 0.1 mM and 2.7 +/- 0.2 mM, respectively), suggesting that EAA nerve terminals in the hippocampus may be selectively vulnerable to oxidative stress.


Asunto(s)
Envejecimiento/metabolismo , Aminoácidos/metabolismo , Química Encefálica/fisiología , Estrés Fisiológico/metabolismo , Animales , Ácido Aspártico/metabolismo , Química Encefálica/efectos de los fármacos , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético/efectos de los fármacos , Glutamatos/metabolismo , Ácido Glutámico , Técnicas In Vitro , Masculino , Proteínas del Tejido Nervioso/metabolismo , Oxidación-Reducción , Potasio/farmacología , Ratas , Ratas Endogámicas F344 , Cianuro de Sodio/farmacología , Estrés Fisiológico/inducido químicamente , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo
14.
Clin Pharmacol Ther ; 32(5): 612-21, 1982 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6957279

RESUMEN

Human platelets contain two independently regulated forms of the drug conjugating enzyme, phenol sulfotransferase (PST). One form of platelet PST activity is relatively thermolabile (TL) and the other is relatively thermostable (TS). Acetaminophen is a substrate for both the TS and TL forms of PST. Our aim was to determine whether individual variations in platelet PST activity might reflect variations in teh sulfate conjugation of oral acetaminophen. Platelet PST activity was measured in blood samples from 29 randomly selected subjects. There was no significant correlation between the independently regulated activities of the TS and TL forms of PST in the platelets of these subjects (r = 0.16, P less than 0.4). Each of the 29 subjects ingested 10 mg/kg acetaminophen and 24-hr urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were measured. Average 24-hr urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were 2.3%, 46.9%, and 35.0% of the total dose of drug. There were significant correlations between the activities of both the TS and TL forms of platelet PST and the excretion of acetaminophen sulfate expressed as a percentage of the dose of the drug (r = 0.62, P less than 0.001; r = 0.456, P less than 0.02). The correlation coefficient between the TS activity and the excretion of acetaminophen sulfate was significant when the excretion of sulfate conjugate was expressed as a percentage of the sum of acetaminophen plus conjugated metabolites excreted (r = 0.565, P less than 0.002). Our data demonstrate that relative levels of platelet PST activity reflect individual variations in the urinary excretion of the sulfate conjugate of acetaminophen.


Asunto(s)
Acetaminofén/metabolismo , Plaquetas/metabolismo , Sulfurtransferasas/metabolismo , Adulto , Arilsulfotransferasa , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Sulfatos/metabolismo
15.
Gene ; 121(2): 271-8, 1992 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-1446824

RESUMEN

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.


Asunto(s)
Anticuerpos/química , Antígenos CD4/inmunología , Receptores de Interleucina-2/inmunología , Secuencia de Aminoácidos , Animales , Reacciones Antígeno-Anticuerpo , Modulación Antigénica , Secuencia de Bases , Clonación Molecular , Activación de Complemento , Expresión Génica , Humanos , Hibridomas , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Ratones , Datos de Secuencia Molecular , ARN Mensajero/genética , Proteínas Recombinantes de Fusión , Transfección
16.
FEBS Lett ; 421(1): 23-6, 1998 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-9462832

RESUMEN

We cloned the Saccharomyces cerevisiae homologue of mammalian RNase HI, which itself is related to the prokaryotic RNase HII, an enzyme of unknown function and previously described as having minor activity in Escherichia coli. Expression of the corresponding yeast 35 kDa protein (named by us RNase H(35)) in E. coli and immunological analysis proves a close evolutionary relationship to mammalian RNase HI. Deletion of the gene (called RNH35) from the yeast genome leads to an about 75% decrease of RNase H activity in preparations from the mutated, still viable cells. Sequence comparison discriminates this new yeast RNase H from earlier described yeast enzymes, RNase H(70) and RNase HI.


Asunto(s)
Evolución Molecular , Ribonucleasa H/genética , Saccharomyces cerevisiae/enzimología , Secuencia de Aminoácidos , Animales , Escherichia coli/enzimología , Humanos , Mamíferos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Reacción en Cadena de la Polimerasa , Ribonucleasa H/química , Alineación de Secuencia , Homología de Secuencia de Aminoácido
17.
FEBS Lett ; 450(3): 251-6, 1999 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-10359084

RESUMEN

We purified Saccharomyces cerevisiae RNase H(70) to homogeneity, using an optimized chromatographic purification procedure. Renaturation gel assay assigned RNase H activity to a 70 kDa polypeptide. Sequencing of tryptic peptides identified the open reading frame YGR276c on chromosome VII of the S. cerevisiae genome as the corresponding gene, which encodes a putative polypeptide of molecular mass of 62849. We therefore renamed this gene RNH70. Immunofluorescence microscopy using a RNH70-EGFP fusion construct indicates nuclear localization of RNase H(70). Deletion of RNH70 from the yeast genome did not result in any serious phenotype under the conditions tested. Homology searches revealed striking similarity with a number of eukaryotic proteins and open reading frames, among them the chimpanzee GOR protein, a homolog of a human autoimmune antigen, found to elicit autoimmune response in patients infected with hepatitis C virus.


Asunto(s)
Ribonucleasa H/aislamiento & purificación , Saccharomyces cerevisiae/enzimología , Secuencia de Aminoácidos , Animales , Núcleo Celular , Células Eucariotas , Genes Fúngicos , Genoma Fúngico , Humanos , Datos de Secuencia Molecular , Fenotipo , Ribonucleasa H/genética , Saccharomyces cerevisiae/genética , Homología de Secuencia de Aminoácido
18.
J Comp Neurol ; 405(4): 543-52, 1999 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-10098944

RESUMEN

We present the first three-dimensional map of the antennal lobe of Drosophila melanogaster, based on confocal microscopic analysis of glomeruli stained with the neuropil-specific monoclonal antibody nc82. The analysis of confocal stacks allowed us to identify glomeruli according to the criteria shape, size, position, and intensity of antibody labeling. Forty glomeruli were labeled by nc82, eight of which have not been described before. Three glomeruli previously shown exclusively by backfills were not discernible in nc82 stainings. We distinguish three classes of glomeruli: (1) "landmark" glomeruli that are constant in all four criteria mentioned above, (2) less well-demarcated glomeruli that deviate in a single criterion, and (3) poorly defined glomeruli that vary in more than one criterion. All class 2 and 3 glomeruli can be identified by comparison with landmark neighbors. To further aid identification, our model assigns glomeruli to five arrays, each of which is defined by a prominent landmark glomerulus. Six glomeruli consist of distinct, but contiguous structural units, termed "compartments." Glomerular variability observed occasionally between males and females is in the same range as between individuals of the same sex, suggesting the lack of a significant sexual dimorphism in the glomerular pattern. We compare the new model with a previous map and address its potential for mapping activity and expression patterns. An important goal of this work was to create three-dimensional reference models of the antennal lobe, which are accessible on-line.


Asunto(s)
Drosophila melanogaster/anatomía & histología , Procesamiento de Imagen Asistido por Computador , Vías Olfatorias/anatomía & histología , Animales , Femenino , Masculino , Microscopía Confocal
19.
J Immunol Methods ; 163(2): 173-9, 1993 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-8102628

RESUMEN

New fluorescent monoclonal antibody-dye conjugates permit three-color immunofluorescence analysis of leukocytes in whole blood using a single laser flow cytometer. The fluorochrome used in this study is a tandem conjugate of phycoerythrin (PE) and Cyan-5, which is excitable at 488 nm with a maximum in the emission spectrum at > 650 nm and it can be used together with PE and fluorescein isothiocyanate (FITC). The directly labelled monoclonal antibodies are incubated with unseparated anticoagulated blood and subsequently erythrocytes are lysed by a standardized automated procedure. The resulting leukocyte suspension can then be analyzed for three different surface markers in an individual sample of 100 microliters blood. When compared simultaneously with single-color analysis triple-color immunofluorescence yielded identical quantitative and qualitative results on various lymphocyte subpopulations. The efficacy of this method was evaluated by analyzing leukocytes of 42 healthy donors for the following markers: CD3, CD4, CD8, CD14, CD16, CD19, CD25, CD38, CD45RO, CD45RA, CD56, CD57, TCR-gamma/delta and HLA-DR. Of special interest was the finding that CD45RA and CD45RO are differently expressed in CD4 and CD8 cells. The reliability and convenience of this three-color analysis will make it possible to do more sophisticated examinations of subpopulations and their relevance in the monitoring of autoimmune diseases, immunodeficiency syndromes including AIDS and malignant disorders such as leukemias.


Asunto(s)
Antígenos CD8/análisis , Citometría de Flujo/métodos , Antígenos Comunes de Leucocito/análisis , Subgrupos Linfocitarios/inmunología , Adulto , Anticuerpos Monoclonales , Antígenos CD/análisis , Linfocitos T CD4-Positivos/inmunología , Femenino , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Antígenos HLA-DR/análisis , Humanos , Inmunofenotipificación , Masculino , Ficoeritrina , Receptores de Antígenos de Linfocitos T gamma-delta/análisis
20.
J Immunol Methods ; 124(1): 121-9, 1989 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-2809224

RESUMEN

The activation of complement components in human serum has been studied using immunoglobulins adsorbed to microtiter plates. The sequential deposition of complement fragments was detected by a series of mono- and polyclonal antibodies in an indirect enzyme-linked immunosorbent assay (ELISA). Antibodies against C1q, C1s, C4b/d, C3b/d, factor B, C5b-9 membrane attack complex (MAC), the regulatory complement proteins C4 binding protein (C4bp) and properdin were reactive. Several lines of evidence suggest that complement activation was via the classical pathway: (1) complement activation was highly isotype-restricted with regard to the adsorbed Igs (human IgG1 and IgG3 as well as mouse IgM, IgG2a and IgG2b isotypes are strong activators in contrast to human IgG2, IgG4, IgA and mouse IgG1); (2) Ca2+ depletion, heat treatment (56 degrees C for 45 min), incubation with 0.5 M KSCN or heat-aggregated immunoglobulins (aggIgG) abrogated serum activity; (3) complement deficient sera (C1q def', C2 def', C6 def' human sera; C2 def', C4 def' guinea pig sera) showed impaired deposition of the complement components that follow the missing component in the cascade of activation. In a clinical study sera from patients with systemic lupus erythematosus (SLE) were investigated in order to measure the effect of hypocomplementemia due to complement consumption. The results obtained suggest that this new and simple assay is well suited for (1) the detection of various inherited complement deficiencies, (2) the semiquantitative evaluation of sera with decreased complement levels, (3) a more detailed study of complement components bound to a solid phase.


Asunto(s)
Activación de Complemento/inmunología , Proteínas del Sistema Complemento/deficiencia , Adsorción , Animales , Anticuerpos/inmunología , Activación de Complemento/fisiología , Proteínas del Sistema Complemento/análisis , Ensayo de Inmunoadsorción Enzimática , Cobayas , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Lupus Eritematoso Sistémico/inmunología , Fragmentos de Péptidos/análisis , Plásticos
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