RESUMEN
To the authors' knowledge, avascular necrosis of the midface secondary to disseminated intravascular coagulation has yet to be described following a hypoxic syncopal episode secondary to 'heat stroke'. A slow, progressive loss of anterior maxillary bone and the collapse of the nasal dorsum in a healthy young man with no other known medical co-morbidities led to the diagnosis. Following debridement, a staged reconstruction of the maxilla-nasal complex was successfully performed.
Asunto(s)
Coagulación Intravascular Diseminada/complicaciones , Coagulación Intravascular Diseminada/diagnóstico , Osteonecrosis/diagnóstico , Osteonecrosis/etiología , Osteonecrosis/cirugía , Adulto , Cefalometría , Desbridamiento , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Tomografía Computarizada por Rayos XRESUMEN
CD4+ T cells are believed to play a central role in the initiation and perpetuation of autoimmune diseases such as multiple sclerosis. In the murine model for multiple sclerosis, experimental autoimmune encephalomyelitis, pathogenic T cells exhibit a Th1-like phenotype characterized by heightened expression of proinflammatory cytokines. Systemic administration of "regulatory" cytokines, which serve to counter Th1 effects, has been shown to ameliorate autoimmune responses. However, the inherent problems of nonspecific toxicity limit the usefulness of systemic cytokine delivery as a potential therapy. Therefore, we used the site-specific trafficking properties of autoantigen-reactive CD4+ T cells to develop an adoptive immunotherapy protocol that provided local delivery of a Th1 cytokine antagonist, the p40 subunit of IL-12. In vitro analysis demonstrated that IL-12 p40 suppressed IFN-gamma production in developing and effector Th1 populations, indicating its potential to modulate Th1-promoted inflammation. We have previously demonstrated that transduction of myelin basic protein-specific CD4+ T cells with pGC retroviral vectors can result in efficient and stable transgene expression. Therefore, we adoptively transferred myelin basic protein-specific CD4+ T cells transduced to express IL-12 p40 into mice immunized to develop experimental autoimmune encephalomyelitis and demonstrated a significant reduction in clinical disease. In vivo tracking of bioluminescent lymphocytes, transduced to express luciferase, using low-light imaging cameras demonstrated that transduced CD4+ T cells trafficked to the central nervous system, where histological analysis confirmed long-term transgene expression. These studies have demonstrated that retrovirally transduced autoantigen-specific CD4+ T cells inhibited inflammation and promoted immunotherapy of autoimmune disorders.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/trasplante , Encefalomielitis Autoinmune Experimental/terapia , Inmunoterapia Adoptiva/métodos , Interleucina-12/administración & dosificación , Células 3T3 , Animales , Autoantígenos/inmunología , Linfocitos T CD4-Positivos/patología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Línea Celular , Movimiento Celular/genética , Movimiento Celular/inmunología , Células Cultivadas , Encefalomielitis Autoinmune Experimental/etiología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/prevención & control , Epítopos de Linfocito T/administración & dosificación , Epítopos de Linfocito T/genética , Regulación de la Expresión Génica/inmunología , Cobayas , Humanos , Interferón gamma/antagonistas & inhibidores , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-12/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteína Básica de Mielina/administración & dosificación , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/inmunología , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/biosíntesis , Receptores de Antígenos de Linfocitos T/genética , Retroviridae/genética , Médula Espinal/inmunología , Médula Espinal/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Transducción Genética , Transfección , Transgenes/inmunologíaRESUMEN
Brain extraction of (18)F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) was significantly higher in pentylene tetrazole (PTZ)-treated rats (32 +/- 4%) than controls (25 +/- 4%). The FDG permeability-surface area product (PS) was also significantly higher with PTZ treatment (0.36 +/- 0.05 ml. min(-1). g(-1)) than in controls (0.20 +/- 0.06 ml. min(-1). g(-1)). Cerebral blood flow rates were also elevated by 50% in seizures. The internal carotid artery perfusion technique indicated mean [(14)C]glucose clearance (and extraction) was increased with PTZ treatment, and seizures increased the PS by 37 +/- 16% (P < 0.05) in cortical regions. Because kinetic analyses suggested the glucose transporter half-saturation constant (K(m)) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities (V(max)) and 3) a single K(m). In cortex, the glucose transporter V(max) was 42 +/- 11% higher (P < 0.05) in PTZ-treated animals (2.46 +/- 0.34 micromol. min(-1). g(-1)) than in control animals (1.74 +/- 0.26 micromol. min(-1). g(-1)), and the K(m) = 9.5 +/- 1.6 mM. Blood-brain barrier (BBB) V(max) was 31 +/- 10% greater (P < 0.05) in PTZ-treated (2.36 +/- 0. 30 micromol. min(-1). g(-1)) than control subcortex (1.80 +/- 0.25 micromol. min(-1). g(-1)). We conclude acute upregulation of BBB glucose transport occurs within 3 min of an initial seizure. Transporter V(max) and BBB glucose permeability increase by 30-40%.