RESUMEN
In this paper we attempt to sharpen and to provide an answer to the question of when human beings first become conscious. Since it is relatively uncontentious that a capacity for raw sensation precedes and underpins all more sophisticated mental capacities, our question is tantamount to asking when human beings first have experiences with sensational content. Two interconnected features of our argument are crucial. First, we argue that experiences with sensational content are supervenient on facts about electrical activity in the cerebral cortex which can be ascertained through EEG readings. Second, we isolate from other notions of a 'functioning brain' that which is required to underpin the view that a cortex is functioning in a way which could give rise to rudimentary conscious experiences. We investigate the development in the human fetus of the anatomical and chemical pathways which underpin (immature) cortical activity and the growth and maturation of the electrical circuitry specifically associated with sensational content in adult experience. We conclude (tentatively) that a fetus becomes conscious at about 30 to 35 weeks after conception; an answer based on a careful analysis of EEG readings at various stages of cortical development. Finally, we survey the possible ethical ramifications of our answer.
Asunto(s)
Comienzo de la Vida Humana , Encéfalo , Desarrollo Embrionario y Fetal , Feto , Vida , Autoimagen , Características Humanas , Humanos , Individualidad , Obligaciones Morales , Personeidad , Responsabilidad Social , Estrés PsicológicoRESUMEN
The expression of three basement membrane components [collagen IV (CIV), laminin and heparan sulphate proteoglycan (HSPG)] and platelet endothelial cell adhesion molecule (PECAM) were examined by immunohistochemistry in cryostat sections of normal human endometrium. Alkaline phosphatase (ALP) was detected using enzyme histochemistry. Endometrial biopsies from the menstrual (n = 4), mid-late proliferative (n = 5), early-mid secretory (n = 5) and late secretory (n = 5) stages were collected from women with a normal menstrual cycle. At all four stages of the menstrual cycle, CIV, laminin and HSPG were expressed on basement membranes of both vessels and glands whilst PECAM expression was localized specifically to endothelial cells. A similar number of vessels/mm2 stained for CIV and laminin, as well as for PECAM at each stage of the menstrual cycle, demonstrating that all vessels in endometrium stain for these two basement membrane components. By contrast, the number of vessels/mm2 that stained positively for HSPG and ALP was significantly lower, averaging approximately 55% of the total that stained positively for PECAM, CIV and laminin. During the menstrual stage, HSPG staining intensity remained strong in glandular basement membranes but decreased dramatically in vascular basement membranes. ALP activity was variable in both the vessels and glands throughout the four stages of the menstrual cycle studied. This study demonstrates heterogeneity in basement membrane components within the endometrial microvasculature. It is postulated that the disappearance of HSPG from vascular basement membranes may play a role in the process of vascular remodelling during the menstrual stage of the cycle.
Asunto(s)
Endometrio/irrigación sanguínea , Ciclo Menstrual , Antígenos de Diferenciación Mielomonocítica/metabolismo , Membrana Basal/metabolismo , Vasos Sanguíneos/metabolismo , Moléculas de Adhesión Celular/metabolismo , Femenino , Humanos , Inmunohistoquímica/métodos , Microcirculación , Tonsila Palatina/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Valores de Referencia , Coloración y Etiquetado , Distribución TisularRESUMEN
In the present study the presence and distribution of cellular adhesion molecules involved in leukocyte binding were investigated in human endometrium. Endometrial biopsies (n = 45) were collected from women at all stages of normal menstrual cycles. Consecutive cryostat sections of endometrium were immunostained with monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule (PECAM) and haematoxylin and eosin. Primary antibody binding was visualized using a streptavidin-biotin system. Strong staining for PECAM was observed in endothelial cells of all vessel types and in focal areas of stroma including single cells, small clusters and larger aggregates of cells. At menstruation, however, almost the entire stroma stained for PECAM which was temporally related to a massive influx of leukocytes. ICAM-1 staining, which was consistently less intense than PECAM staining, was detected in vascular endothelial cells during the cycle, reaching a peak at menstruation. Unlike PECAM, ICAM-1 staining did not occur consistently across all vessel types. Stromal staining for ICAM-1 was rare except at menstruation, when almost the entire stroma showed positive staining for ICAM-1. No glandular or luminal epithelial staining was detected for either PECAM or ICAM-1. This study demonstrates that PECAM and ICAM-1 are expressed on endothelial cells of veins, arterioles and capillaries, and stromal cells within human endometrium.
Asunto(s)
Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Moléculas de Adhesión Celular/análisis , Endometrio/química , Ciclo Menstrual/metabolismo , Adulto , Femenino , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Menstruación/metabolismo , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de PlaquetaRESUMEN
Using in vivo microscopy we investigated endometrial microvascular events occurring on days 5 and 6 of pregnancy at the time of implantation. Blood flow through the endometrium was visualized using incident-light fluorescence microscopy and a video image was recorded for subsequent analysis. At 17:00 h on day 5 of pregnancy it was not possible to identify the impending implantation site from the in vivo appearance of the subepithelial capillary plexus. At 09:00 h on day 6 of pregnancy the embryo implantation site was recognized as an avascular area surrounded by large diameter vessels. These were highly susceptible to haemorrhage when handled. Capillaries closest to the embryo had the greatest diameters, averaging 18.5 +/- 2.5 microns, and capillary diameters decreased to 7.5 +/- 0.4 microns by 2000 microns from the embryo. It was also observed that blood flow through larger diameter vessels was sluggish with frequent reversals and stoppages. Leucocyte rolling and adhesion were also common features in these larger vessels. These data indicate that changes in capillary diameter occur in response to local signals associated with the implanting rat embryo. The embryonic or local endometrial signals that mediate these major microvascular changes remain to be elucidated.
Asunto(s)
Implantación del Embrión , Endometrio/irrigación sanguínea , Preñez/fisiología , Análisis de Varianza , Animales , Velocidad del Flujo Sanguíneo , Capilares/ultraestructura , Femenino , Microcirculación , Microscopía Fluorescente , Embarazo , Ratas , Ratas Sprague-Dawley , Análisis de Regresión , Grabación de Cinta de VideoRESUMEN
The effect of leupeptin, a serine protease inhibitor, on the fertilization and development potential of oocytes stimulated to undergo cortical granule exocytosis has been investigated. An in-vitro bioassay system was used in which mouse oocytes were exposed to calcium ionophore, A23187, in the presence and absence of leupeptin, before their fertilization and development to the blastocyst stage was assessed. We have demonstrated that the presence of leupeptin in the incubation medium, at concentrations of 1 micrograms/ml and 10 micrograms/ml during the first 10 min of cortical granule exocytosis, reversed the ionophore-induced decrease in the capacity of oocytes to fertilize and develop to blastocysts. The induction of exocytosis of cortical granules by calcium ionophore was confirmed using fluorescence microscopy. Using this technique, we also confirmed that leupeptin did not inhibit ionophore-induced cortical granule exocytosis, thus supporting the contention that leupeptin acted upon released cortical exudate. It was concluded that leupeptin acted by inhibiting proteases released into the perivitelline space during the early stages of cortical granule exocytosis. Based on these results it was proposed that leupeptin could be used to prevent premature loss of fertility of human oocytes which are inadvertently activated under in-vitro conditions.