RESUMEN
Therapeutic hypothermia (TH) improves the neurological outcome in experimental brain trauma models as well as in patients suffering from cardiac arrest and perinatal asphyxia. So far the efficacy of TH has not been proven in acute ischemic stroke due to lack of clinical data. The EuroHYP-1 study will investigate whether TH with an individual target range temperature between 34 and 35 °C administered for 24 h will improve the neurological outcome in ischemic stroke patients treated within 6 h from symptom onset. The target patient number of 1,500 to be included in EuroHYP-1 is sufficiently powered to detect the efficacy of TH.
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Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Hipotermia Inducida/métodos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/economía , Método Doble Ciego , Europa (Continente) , Unión Europea/economía , Femenino , Humanos , Hipotermia Inducida/economía , Masculino , Persona de Mediana Edad , Efecto Placebo , Accidente Cerebrovascular/economía , Resultado del Tratamiento , Adulto JovenRESUMEN
In line with the National Action Plan "IN FORM" the German Federal Ministry of Health funds the establishment of 11 regional community health promotion networks (alliances). To meet quality development standards, an external evaluation project has been established in addition to the alliances' internal evaluation. Scientific monitoring focuses on alliance-spanning investigation of quality of planning, structures and processes and uses different methods and instruments (e.g., guided interviews, analytical framework, Goal Attainment Scaling). Regional networks also receive support for their efforts to quality development. Up to now concluding analysis can be done on aspects of planning quality based on findings of the analytical framework developed within the project. 5 selected results presented in the article reveal a heterogeneous picture: on one hand the standard on which the alliances' rationales on demands justifying the project's strategy are written at is very encouraging. The situation is similar with the descriptions of the work planning and statements concerning the sustainability at which the implemented activities are aimed. On the other hand, in explaination criteria like consideration of target group's needs or definition of goals the possibilities are not exhausted yet considering the state of the debate. Hence in similar future projects there is a clear necessity of assistance in approaching these aspects, provided preferably in an early stage of the planning phase.
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Servicios de Salud Comunitaria/organización & administración , Servicios de Salud Comunitaria/normas , Implementación de Plan de Salud/organización & administración , Implementación de Plan de Salud/normas , Promoción de la Salud/organización & administración , Promoción de la Salud/normas , Estilo de Vida , Garantía de la Calidad de Atención de Salud/organización & administración , Garantía de la Calidad de Atención de Salud/normas , Indicadores de Calidad de la Atención de Salud/organización & administración , Indicadores de Calidad de la Atención de Salud/normas , Alemania , Necesidades y Demandas de Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/normas , Humanos , Objetivos Organizacionales , Evaluación de Programas y Proyectos de Salud/normasRESUMEN
BACKGROUND: The typical clinical manifestation of an infection with the obligate anaerobic, gram-negative, rod-shaped bacteria Fusobacterium necrophorum is the Lemierre syndrome. As the cause of osteomyelitis and mastoiditis factors of the normal bacteria flora are more likely to be found than Fusobacterium necrophorum. Nevertheless, Necrobacillosis is an important differential diagnosis of complicated courses of mastoiditis. MATERIAL AND METHODS: Because the clinical courses of mastoiditis with osteomyelitis may differ a lot, making the appropriate diagnosis more difficult, consistently and flawless detection of the pathogens is important. Therefore a correct specimen collection, transportation and the subsequent cultivation of the pathogens is essential. RESULTS: The genus Fusobacterium is an obligate anaerobic, gram-negative rod-shaped bacteria. Infections involving the genus Fusobacterium are usually formed endogenously. They are characterized by subacute to chronic, purulent gangrenous necrotizing inflammations. CONCLUSION: As a differential diagnosis, infections with Streptococcus spp., Haemophilus influenzae, Branhamella catarrhalis and Staphylococcus aureus are more likely to cause mastoiditis and osteomyelitis than an infection with Fusobacterium necrophorum. However, the infection with this fusiform bacillus is possible under pathological circumstances e.g. deficiency syndroms, so that when observing a prolonged disease course of mastoiditis an infection with Fusobacterium necrophorum should be considered .
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Infecciones por Fusobacterium/diagnóstico , Fusobacterium necrophorum , Mastoiditis/diagnóstico , Osteomielitis/diagnóstico , Base del Cráneo , Hueso Temporal , Trastornos de la Articulación Temporomandibular/diagnóstico , Antibacterianos/uso terapéutico , Técnicas Bacteriológicas , Terapia Combinada , Desbridamiento , Diagnóstico Diferencial , Infecciones por Fusobacterium/terapia , Humanos , Síndrome de Lemierre/diagnóstico , Síndrome de Lemierre/terapia , Mastoiditis/terapia , Pruebas de Sensibilidad Microbiana , Osteomielitis/terapia , Otitis Media/diagnóstico , Otitis Media/terapia , Trastornos de la Articulación Temporomandibular/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The best known clinical picture of a one-sided necrotisising, infectious tonsillitis is the by Plaut and Vincent (1894) described angina Plaut-Vincent. In addition to this fusospirochetosis it is in case of necrotisising inflammations in the oropharynx differential-diagnostically important to consider also the anaerobic type Prevotella, especially Prevotella disiens as a potential trigger . MATERIAL AND METHODS: Because the clinical course forms of a necrotisising oropharyngeal inflammations can be very different and complicate so a suitable diagnosis, it is very important to get a complete and perfect cause proof. For getting this proof a correct test production, transport and cultivation are of extreme importance . RESULTS: The type Prevotella consists of different species gram-negative, obligate anaerobic strains. They are regarded as a cause of suppurating inflammations and abscesses of the genital tract and are components of the aerobic anaerobic mixed flora in case of gingival infections. The sole proof in the microbiological culture as a smear test result of a one-sided necrotisising tonsillitis has to be seen as a first description by reason of missing literature . IMPLICATION: As triggers for one-sided necrotisising tonsillitis are considered different causes. Next a carcinoma of the tonsil, Lues, Angina Plaut-Vincent have to be excluded. An infection with Prevotella disiens is an extremely rare variation in contrast. However, the transmission is possible by insufficient hygiene, lack phenomena and sexual intercourse and to consider therefore as an exclusion diagnosis.
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Infecciones Bacterianas/diagnóstico , Tonsila Palatina/patología , Tonsilitis/diagnóstico , Antibacterianos/uso terapéutico , Infecciones Bacterianas/patología , Infecciones Bacterianas/terapia , Técnicas Bacteriológicas , Infecciones por Bacteroidaceae/diagnóstico , Infecciones por Bacteroidaceae/patología , Infecciones por Bacteroidaceae/terapia , Diagnóstico Diferencial , Infecciones por Fusobacterium/diagnóstico , Infecciones por Fusobacterium/patología , Infecciones por Fusobacterium/terapia , Gingivitis Ulcerosa Necrotizante/diagnóstico , Gingivitis Ulcerosa Necrotizante/patología , Gingivitis Ulcerosa Necrotizante/terapia , Humanos , Necrosis , Úlceras Bucales/diagnóstico , Prevotella , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Sífilis/patología , Tonsilectomía , Tonsilitis/patología , Tonsilitis/terapiaRESUMEN
BACKGROUND: Glial neoplasms can infiltrate the central nervous system extensively with relative preservation of the underlying neuronal architecture. The differential diagnosis between cerebral glioma and infective lesions can be very difficult to distinguish by MRI only. CASE REPORT: We report a 7 year old boy with recurrent vomiting, fever, weakness, abdominal pain and diarrhea. Besides an expressive speech disturbance the neurological examination showed no pathological findings. The sonography revealed discrete hepatomegaly and small pericardial effusion. MRI showed a diffuse mesencephalic and pontine swelling without contrast medium enhancement possibly pointing to an infective lesion. Microbiological, serological and metabolic investigations of blood and CSF were normal. After initial improvement associated with antibiotic, antiviral and dexamethasone treatment the process relapsed progessively. The 1H-MR-spectroscopy showed elevated cholin and decreased N-acetyl-aspartate levels suspicious for a proliferating process. Brain biopsy revealed anaplastic astrocytoma (WHO III). Despite of radiation and chemotherapy the tumordisease deteriorated and the patient died because of progressive brainstem infiltration one year later. CONCLUSION: This case report shows that cerebral glioma can mimick infective brain disease and that MR-spectroscopy is an important non-invasive tool in this differential diagnosis.
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Astrocitoma/diagnóstico , Neoplasias del Tronco Encefálico/diagnóstico , Neoplasias Cerebelosas/diagnóstico , Encefalitis/diagnóstico , Espectroscopía de Resonancia Magnética , Puente , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Niño , Colina/análisis , Creatina/análisis , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under "baseline" conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline "plaques" (71% and 3%), plus unusual "string" (14%), "ribbon" (7%) and "reticular" (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina.
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Uniones Comunicantes/ultraestructura , Vías Nerviosas/ultraestructura , Neuronas/ultraestructura , Retina/ultraestructura , Animales , Comunicación Celular/fisiología , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Femenino , Técnica de Fractura por Congelación , Uniones Comunicantes/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Microscopía Inmunoelectrónica , Modelos Neurológicos , Vías Nerviosas/fisiología , Neuronas/fisiología , Estimulación Luminosa , Ratas , Ratas Sprague-Dawley , Retina/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiología , Células Fotorreceptoras Retinianas Bastones/ultraestructura , Visión Ocular/fisiologíaRESUMEN
Most gap junctions between neurons in mammalian retina contain abundant connexin36, often in association with the scaffolding protein zonula occludens-1. We now investigate co-association of connexin36, zonula occludens-1, zonula occludens-2 and Y-box transcription factor 3 (zonula occludens-1-associated nucleic acid-binding protein) in mouse and rat retina. By immunoblotting, zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were both detected in retina, and zonula occludens-2 in retina was found to co-immunoprecipitate with connexin36. By immunofluorescence, the four proteins appeared as puncta distributed in the plexiform layers. In the inner plexiform layer, most connexin36-puncta were co-localized with zonula occludens-1, and many were co-localized with zonula occludens-1-associated nucleic acid-binding protein. Moreover, zonula occludens-1-associated nucleic acid-binding protein was often co-localized with zonula occludens-1. Nearly all zonula occludens-2-puncta were positive for connexin36, zonula occludens-1 and zonula occludens-1-associated nucleic acid-binding protein. In the outer plexiform layer, connexin36 was also often co-localized with zonula occludens-1-associated nucleic acid-binding protein. In connexin36 knockout mice, labeling of zonula occludens-1 was slightly reduced in the inner plexiform layer, zonula occludens-1-associated nucleic acid-binding protein was decreased in the outer plexiform layer, and both zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were markedly decreased in the inner sublamina of the inner plexiform layer, whereas zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated nucleic acid-binding protein puncta persisted and remained co-localized in the outer sublamina of the inner plexiform layer. By freeze-fracture replica immunogold labeling, connexin36 was found to be co-localized with zonula occludens-2 within individual neuronal gap junctions. In addition, zonula occludens-1-associated nucleic acid-binding protein was abundant in a portion of ultrastructurally-defined gap junctions throughout the inner plexiform layer, and some of these junctions contained both connexin36 and zonula occludens-1-associated nucleic acid-binding protein. These distinct patterns of connexin36 association with zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated nucleic acid-binding protein in different sublaminae of retina, and differential responses of these proteins to connexin36 gene deletion suggest differential regulatory and scaffolding roles of these gap junction accessory proteins. Further, the persistence of a subpopulation of zonula occludens-1/zonula occludens-2/zonula occludens-1-associated nucleic acid-binding protein co-localized puncta in the outer part of the inner plexiform layer of connexin36 knockout mice suggests close association of these proteins with other structures in retina, possibly including gap junctions composed of an as-yet-unidentified connexin.
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Conexinas/metabolismo , Proteínas de Unión al ADN/metabolismo , Uniones Comunicantes/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Retina/metabolismo , Animales , Calbindina 2 , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Conexinas/genética , Proteínas de Unión al ADN/genética , Femenino , Técnica del Anticuerpo Fluorescente , Técnica de Fractura por Congelación , Uniones Comunicantes/ultraestructura , Inmunohistoquímica , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Rastreo , Neuronas/metabolismo , Neuronas/ultraestructura , Fosfoproteínas/genética , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Proteínas de Unión al ARN/genética , Ratas , Ratas Sprague-Dawley , Retina/ultraestructura , Proteína G de Unión al Calcio S100/metabolismo , Proteína de la Zonula Occludens-1 , Proteína de la Zonula Occludens-2 , Proteína delta-6 de Union ComunicanteRESUMEN
The ex-utero intra-partum (EXIT) procedure enables the surgeon to perform invasive procedures in an infant during cesarean section before clamping the umbilical cord. Specific anesthesiological concepts are necessary for ensuring sufficient umbilical perfusion. We report the case of a 33-year-old female undergoing cesarean section in the 36th week of pregnancy because of a large fetal cervical tumor. The EXIT procedure was performed in order to secure the infant's airway during delivery. The anesthesiological management and interdisciplinary tasks are discussed in the literature review.
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Anestesia , Neoplasias del Cuello Uterino/cirugía , Adulto , Cesárea , Femenino , Humanos , Recién Nacido , Monitoreo Intraoperatorio , Embarazo , Respiración Artificial , Cordón Umbilical/fisiologíaRESUMEN
In patients with propionic aciduria, the accumulating metabolite propionyl-CoA causes a disturbance of the urea cycle via the inhibition of N-acetylglutamate synthesis. Lack of this allosteric activator results in an inhibition of carbamoylphosphate synthase (CPS). This finally leads to hyperammonaemia. In two patients with decompensated propionic aciduria the CPS activator carbamylglutamate was tested for its ability to antagonize the propionyl-CoA associated hyperammonaemia. Oral carbamyl glutamate administration resulted in a significant increase in ammonia detoxification and could avoid further dialysis therapy. Safe, fast and easy to administer, carbamyl glutamate improves the acute therapy of decompensated propionic aciduria by increasing ammonia detoxification and avoiding hyperammonaemia.
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Glutamatos/administración & dosificación , Hiperamonemia/tratamiento farmacológico , Hiperamonemia/orina , Errores Innatos del Metabolismo/tratamiento farmacológico , Errores Innatos del Metabolismo/orina , Propionatos/orina , Humanos , Hiperamonemia/etiología , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/orina , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Herpes simplex virus type 1 (HSV-1) is latent in the nervous system of most humans. Ball [Can J Neurol Sci 9 (1982) 303] first suggested the hypothesis that HSV-1 could be involved in the pathogenesis of Alzheimer's Disease (AD) by noting that regions of the brain particularly and earliest affected in AD were the same as those most damaged during HSV encephalitis. Data from Itzhaki's research suggests that HSV-1 in the brain and the carriage of an apolipoprotein E allele 4 (ApoE e4) together confer risk for AD [J Pathol 97 (2002) 395], [Mol Chem Neuropathol 28 (1996) 135], [Alzheimer's Rep 1 (1998) 173], [Biochem Soc Trans 26 (1998) 273]. Of the two other studies based on Itzhaki's findings, one showed similar results [Lancet 349 (1997) 1102], and the other showed a similar trend [Lancet 351 (1998) 1330], [Lancet 352 (1998) 1312]. To further examine the role of HSV-1 in the etiology of AD, we have formulated a Neuroinvasive Score that quantifies the presence and viral load of HSV-1 in eight brain regions. These regions are: entorhinal cortex, hippocampus, pons, cerebellum, and neocortex (temporal, parietal, occipital, and frontal). We hypothesize that the Neuroinvasive Score that encompasses the presence, amount, and extent of HSV-1 spreading (neuroinvasiveness), will correlate with the genetic risk factor, ApoE e4, in the assessment of autopsy samples from AD patients. If the neuroinvasive score can be directly correlated to the different stages of AD (mild, moderate, severe), this will strengthen the hypothesis that HSV-1 is involved in AD and that ApoE e4 also confers risk for the development and progression of AD.
Asunto(s)
Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/virología , Encéfalo/virología , Herpesvirus Humano 1 , Carga Viral/métodos , Humanos , Factores de RiesgoRESUMEN
Keratocytes express MHC class I molecules constitutively, and keratocytes stimulated with IFN-gamma express MHC class II molecules. Unstimulated keratocytes constitutively express B7-1 and ICAM-1, as well as low levels of CD40 and 4-1BBL. These findings indicate that keratocytes may deliver both antigen-specific and costimulatory signals to CD4(+) and CD8(+) T cells. To demonstrate that keratocytes expressing B7-1 provide a costimulatory signal to T cells, CD4(+) or CD8(+) mouse T cells were incubated with anti-CD3 mAb and irradiated keratocytes. Enhanced proliferation of both CD4(+) and CD8(+) T cells occurred, and could be inhibited by anti-B7-1 mAb, indicating T cell costimulatory activity by B7-1 on the keratocytes. To demonstrate that keratocytes can deliver an antigen-specific signal, CD4(+) and CD8(+) T cells from herpes-infected mice were incubated with HSV-1-infected, irradiated keratocytes. The resulting T cell proliferation and production of Th1 cytokines (IL-2, IFN-gamma) indicated T cell activation by antigens presented by the infected keratocytes. These results show that keratocytes in the corneal stroma of the mouse can function as antigen-presenting cells and, thus, may play a role in immune-mediated stromal inflammation such as herpetic stromal keratitis.
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Células Presentadoras de Antígenos/fisiología , Córnea/citología , Animales , Antígenos CD/análisis , Antígeno B7-1/análisis , Antígeno B7-2 , Antígenos CD40/análisis , Células Cultivadas , Citocinas/biosíntesis , Femenino , Antígenos de Histocompatibilidad Clase II/análisis , Queratitis/inmunología , Activación de Linfocitos , Glicoproteínas de Membrana/análisis , Ratones , Ratones Endogámicos BALB C , Células del Estroma/fisiologíaRESUMEN
We hypothesized that non-proliferating (quiescent) human vascular endothelial cells would not express somatostatin receptor subtype 2 (sst 2) and that this receptor would be expressed when the endothelial cells begin to grow. To test this hypothesis, placental veins were harvested from 6 human placentas and 2 mm vein disks were cultured in 0.3% fibrin gels. Morphometric analysis confirmed that 50-75% of cultured vein disks developed radial capillary growth within 15 days. Sst 2 gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the RNA from veins before culture and from tissue-matched vein disks that exhibited an angiogenic response. The sst 2 gene was expressed in the proliferating angiogenic sprouts of human vascular endothelium. The presence of sst 2 receptors on proliferating angiogenic vessels was confirmed by immunohistochemical staining and in vivo scintigraphy. These results suggest that sst 2 may be a unique target for antiangiogenic therapy with sst 2 preferring somatostatin analogues conjugated to radioisotopes or cytotoxic agents.
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Endotelio Vascular/metabolismo , Receptores de Somatostatina/metabolismo , Animales , Secuencia de Bases , Células Cultivadas , Técnicas de Cultivo , Cartilla de ADN , Endotelio Vascular/citología , Expresión Génica , Humanos , Inmunohistoquímica , Ratones , Ratones Desnudos , Neovascularización Fisiológica , Receptores de Somatostatina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Herpes simplex virus type 1 (HSV-1) is a prevalent microbial pathogen infecting 60% to 90% of the adult world population. The co-evolution of the virus with humans is due, in part, to adaptations that the virus has evolved to aid it in escaping immune surveillance, including the establishment of a latent infection in its human host. A latent infection allows the virus to remain in the host without inducing tissue pathology or eliciting an immune response. During the acute infection or reactivation of latent virus, the immune response is significant, which can ultimately result in corneal blindness or fatal sporadic encephalitis. In fact, HSV-1 is one of the leading causes of infectious corneal blindness in the world as a result of chronic episodes of viral reactivation leading to stromal keratitis and scarring. Significant inroads have been made in identifying key immune mediators that control ocular HSV-1 infection and potentially viral reactivation. Likewise, viral mechanisms associated with immune evasion have also been identified and will be discussed. Lastly, novel therapeutic strategies that are currently under development show promise and will be included in this review. Most investigators have taken full advantage of the murine host as a viable working in vivo model of HSV-1 due to the sensitivity and susceptibility to viral infection, ease of manipulation, and a multitude of developed probes to study changes at the cellular and molecular levels. Therefore, comments in this review will primarily be restricted to those observations pertaining to the mouse model and the assumption (however great) that similar events occur in the human condition.
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Queratitis Herpética/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Citocinas/genética , Ojo/inmunología , Terapia Genética , Herpesvirus Humano 1/inmunología , Humanos , Inmunidad Celular , Vigilancia Inmunológica , Queratitis Herpética/prevención & control , Queratitis Herpética/terapia , RecurrenciaRESUMEN
BACKGROUND: Gillespie syndrome is the phenotype partial aniridia, cerebellar ataxia and mental retardation. Further malformations can be associated, mainly females are affected. Inheritance and genetics of the syndrome are unknown. Autosomal dominant aniridia is an important differential diagnosis of fixed dilated pupils and is usually associated by mutations of the PAX6 gene. In 1998 the first report of a chromosomal abnormality presenting a de novo translocation t(X;11) (p22.32;p12) detected in a patient with Gillespie syndrome has been published. PATIENTS AND METHODS: A 8 year-old girl with Gillespie syndrome phenotype associated with congenital pulmonary stenosis and helix dysplasia is reported. Karyotyping as well as molecular biological investigations of the PAX6 gene were performed. RESULTS: The karyotype of the girl and her clinically inconspicuous mother showed no abnormalities, especially no de novo translocation of the chromosomes X and 11. PAX6 gene analysis of the affected girl presented no mutations. CONCLUSIONS: The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Congenital pulmonary stenosis and helix dysplasia can be associated. PAX6 gene analysis can be helpful to distinguish between autosomal dominant aniridia and Gillespie syndrome. To illucidate the underlying genetic defects karyotyping and the search for de novo translocations especially of chromosome X and 11 should be performed.
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Anomalías Múltiples , Cerebelo/anomalías , Proteínas del Ojo/genética , Proteínas de Homeodominio/genética , Discapacidad Intelectual , Iris/anomalías , Anomalías Múltiples/genética , Cerebelo/patología , Niño , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Femenino , Humanos , Iris/patología , Cariotipificación , Imagen por Resonancia Magnética , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box , Fenotipo , Reacción en Cadena de la Polimerasa , Proteínas Represoras , Síndrome , Translocación GenéticaRESUMEN
An understanding of the cellular genes whose expression is altered during HSV reactivation will enable us to better understand host responses and biochemical pathways involved in the process. Furthermore, this knowledge could allow us to develop gene-targeted inhibitors to prevent viral reactivation. Mice latent with HSV-1 strain McKrae and uninfected control mice were subjected to hyperthermic stress (43 degrees C for 10 min) and their trigeminal ganglia (TG) collected 1 h later. Two additional groups included HSV-1 latently infected and uninfected mice not subjected to hyperthermic stress. Poly A+ mRNA was enriched from total mouse TG RNA and reverse transcribed using MMLV RT. Radioactively labeled cDNAs were analyzed by microarray analysis. A stress/toxicology array of 149 mouse genes on a nylon membrane was used. The labeled cDNAs prepared from latently infected, stressed mice demonstrated 3-fold or greater increases in certain mRNA-early response genes (ERGs) compared to cDNAs from uninfected, stressed control mice. The ERG mRNAs that showed increases included two heat shock proteins (HSP60 and HSP40), a basic transcription factor (BTF T62), a DNA repair enzyme, two kinases [MAP kinase and a stress-induced protein kinase (SADK)], an oxidative stress-induced protein, a manganese superoxide dismutase precursor-2 (SOD-2), and cyclooxygenase 2 (COX-2). The gene expression in unstressed, infected TGs was similar to the gene expression in unstressed, uninfected controls. These results suggest that there is a significant difference in the ERG expression profile in latently infected TGs undergoing stress-induced reactivation compared to uninfected TGs.
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Expresión Génica , Herpesvirus Humano 1/genética , Ganglio del Trigémino/metabolismo , Latencia del Virus , Animales , Femenino , Perfilación de la Expresión Génica , Herpesvirus Humano 1/fisiología , Hipertermia Inducida , Ratones , Ratones Endogámicos BALB C , Análisis de Secuencia por Matrices de Oligonucleótidos , Activación ViralRESUMEN
A male infant is described who presented with persistent hyperinsulinaemic hypoglycaemia, responding to diazoxide treatment. However, this therapy was discontinued because of seizures as a consequence of disturbed water and electrolyte balance. Glucose homeostasis could only be maintained by subtotal pancreatectomy, which was performed at 3 8/12 years of age. He developed a severe thrombosis, whereon a congenital disorder of glycosylation (CDG) was suspected. An abnormal transferrin isoelectric focusing pattern was found and the diagnosis of CDG Ia was confirmed by enzyme and molecular genetic analysis. This is the first patient with phosphomannomutase deficiency (McKusick 601785) described presenting with severe hyperinsulinaemic hypoglycaemia.
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Trastornos Congénitos de Glicosilación/complicaciones , Hiperinsulinismo/etiología , Hipoglucemia/etiología , Fosfotransferasas (Fosfomutasas)/deficiencia , Preescolar , Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/enzimología , Trastornos Congénitos de Glicosilación/genética , Humanos , Lactante , Masculino , Fosfotransferasas (Fosfomutasas)/genéticaRESUMEN
UNLABELLED: Optimal cancer radiotherapy using Auger electron emitters requires selective localization of radionuclides in close proximity to tumor DNA. METHODS: Intracellular trafficking of (125)I-Tyr1-somatostatin-14 somatotropin-release inhibiting factor (SRIF) and 2 of its analogs, (125)I-WOC 4a and (111)In-pentetreotide, was studied in human neuroblastoma cells. RESULTS: After 24-h incubation, SRIF was degraded or recycled, whereas its protease-resistant analogs progressively accumulated in nuclear fractions. (111)In-pentetreotide binding to DNA increased over time in somatostatin receptor-positive cells but not in somatostatin receptor-negative cells. CONCLUSION: These in vitro studies show that prolonged exposure to radiolabeled SRIF analogs significantly increases their cellular internalization, nuclear translocation, and DNA binding. Clinically, infusion of radiolabeled somatostatin analogs may enhance tumor uptake and retention and provide more effective in situ radiotherapy.
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Núcleo Celular/metabolismo , Neuroblastoma/metabolismo , Tirosina/análogos & derivados , ADN de Neoplasias/metabolismo , Humanos , Indio/farmacocinética , Neuroblastoma/ultraestructura , Compuestos Organometálicos/farmacocinética , Unión Proteica , Somatostatina/análogos & derivados , Somatostatina/análisis , Somatostatina/farmacocinética , Células Tumorales Cultivadas/metabolismo , Tirosina/farmacocinéticaRESUMEN
Herpes simplex virus (HSV) is neurotropic and can pass from neuron to neuron at nerve terminals. During the long evolutionary relationship between HSV and vertebrates, this virus may have evolved surface ligands that mimic nerve cell receptors. The present study was undertaken to determine if herpes simplex virus type 1 (HSV-1) has an antigenic relationship with the acetylcholine receptor (AChR). Mice immunized with HSV-1 antigens or an AChR-expressing cell line were tested for antibodies directed against the AChR. By flow cytometry and ELISA, mouse anti-HSV-1 sera were found to contain antibodies that would bind to an epitope on the plasma membrane of AChR-expressing cells. Mice immunized with the AChR-expressing cells were tested for their resistance to HSV-1 infection. Statistically significantly more of the animals immunized with AChR-expressing cells resisted infection and fatal encephalitis, compared to control animals immunized with a cell line not expressing the AChR. Sera from AChR-immunized mice were tested for anti-HSV antibody by ELISA and were found to contain antibodies cross-reactive with HSV-1 antigens. These sera also neutralized virus in a plaque inhibition assay. The results indicate that there are one or more antigenic epitopes shared by herpesvirus and the AChR. Studies are in progress to define the pathogenetic significance of this molecular mimicry.
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Antígenos Virales/inmunología , Herpesvirus Humano 1/inmunología , Receptores Colinérgicos/inmunología , Animales , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos BALB CRESUMEN
The peripheral blood cells from a patient with a B-cell lymphoma were established in long-term tissue culture. Two years after establishment of the cells in culture they were infected with herpes simplex virus type 2 and the productivity and duration of viral persistence investigated. One week after infection the lymphoblastoid cells were productively infected and have remained so for a period of over 3 years. Expression of a viral glycoprotein antigen was evaluated by using a fluorescein-labeled monoclonal anti-herpes simplex virus type 2 antibody and revealed a spectrum of staining reactions grading from a lightly stippled to very intense pattern. Polymerase chain reaction analysis of the infected cells revealed the presence of the herpes simplex virus type 2 DNA polymerase gene in the infected cells that was absent from the uninfected lymphoblastoid cells. These results taken together with the long-term growth characteristics of both the infected and uninfected lymphoblastoid cells suggest that this cell line may be a good model system for studying viral infection, viral replication, viral latency, and clinical application for the isolation of human herpes virus.
Asunto(s)
Aberraciones Cromosómicas , Herpesvirus Humano 2/fisiología , Linfoma de Células B/sangre , Linfoma de Células B/virología , Adulto , Técnicas de Cultivo de Célula/métodos , División Celular , Línea Celular , Bandeo Cromosómico , Herpesvirus Humano 2/aislamiento & purificación , Humanos , Cariotipificación , Linfoma de Células B/genética , Linfoma de Células B/patología , Masculino , Reacción en Cadena de la Polimerasa , Células Tumorales CultivadasRESUMEN
Cytokines are hormones once thought to be restricted to the immune system produced solely by hematopoietic-derived cells and acting on receptors expressed by cells of the immune system. However, it is now clear that many cytokines are produced not only by lymphocytes, monocytes, granulocytes, and dendritic cells but are also synthesized by cells outside the realm of the immune system in response to stimuli that may not be associated with immune homeostasis. In fact, there is evidence supporting a role of selected cytokines modifying behavior and neuroendocrine function. Recently, a potential relationship between the cytokine interleukin (IL)-6 and herpes simplex virus type 1 (HSV-1) reactivation has been found. This article discusses the relevance of these findings and considers the potential impact that HSV-1 infection has on behavior and chronic inflammatory processes that can occur in the nervous system during "latent" virus infection as a result of chronic IL-6 expression.