RESUMEN
Several immune-based approaches are being considered for modulation of inflammatory T cells and amelioration of autoimmune diseases. The most recent strategies include simulation of peripheral self-tolerance by injection of adjuvant free antigen, local delivery of cytokines by genetically altered T cells, and interference with the function of costimulatory molecules. Although promising results have been obtained from these studies that define mechanisms of T cell modulation, efficacy, practicality, and toxicity, concerns remain unsolved, thereby justifying further investigations to define alternatives for effective downregulation of aggressive T cells. In prior studies, we demonstrated that an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP)1 peptide corresponding to amino acid sequence 139-151 of PLP, Ig-PLP1, is presented to T cells approximately 100-fold better than free PLP1. Here, we demonstrate that aggregation endows Ig-PLP1 with an additional feature, namely, induction of interleukin (IL)-10 production by macrophages and dendritic cells, both of which are antigen-presenting cells (APCs). These functions synergize in vivo and drive effective modulation of autoimmunity. Indeed, it is shown that animals with ongoing active experimental allergic encephalomyelitis dramatically reduce the severity of their paralysis when treated with adjuvant free aggregated Ig-PLP1. Moreover, IL-10 displays bystander antagonism on unrelated autoreactive T cells, allowing for reversal of disease involving multiple epitopes. Therefore, aggregated Ig-PLP1 likely brings together a peripheral T cell tolerance mechanism emanating from peptide presentation by APCs expressing suboptimal costimulatory molecules and IL-10 bystander suppression to drive a dual-modal T cell modulation system effective for reversal of autoimmunity involving several epitopes and diverse T cell specificities.
Asunto(s)
Encefalomielitis Autoinmune Experimental/terapia , Tolerancia Inmunológica , Interleucina-10/biosíntesis , Lipoproteínas/uso terapéutico , Proteínas de la Membrana/uso terapéutico , Proteína Proteolipídica de la Mielina , Vaina de Mielina/inmunología , Linfocitos T/inmunología , Animales , Complejo Antígeno-Anticuerpo/uso terapéutico , Células Presentadoras de Antígenos/inmunología , Regulación hacia Abajo , Epítopos , Inmunoterapia , Interferón gamma/biosíntesis , Activación de Linfocitos , Ratones , Parálisis/terapia , SolubilidadRESUMEN
Catfish, described as 'swimming tongues', are unique experimental models for studies of taste reception because of the extensive distribution of taste buds over their external body surface and within their oropharyngeal cavity. Both the extraordinary numbers of taste buds and their high sensitivity to amino acids have made it possible to perform in the same species: biochemical and biophysical studies of stimulus recognition and signal transduction; electrophysiological recordings of taste activity from receptor cells, afferent nerve fibers and CNS relays; and behavioral studies of taste-controlled food search, biting and mastication. The close correspondence of results obtained with these diverse experimental approaches has provided critical information concerning vertebrate gustation.
Asunto(s)
Aminoácidos , Células Quimiorreceptoras/fisiología , Ictaluridae/fisiología , Gusto/fisiología , Animales , Nervio Facial/fisiología , Conducta Alimentaria/fisiología , Proteínas de Unión al GTP/fisiología , Ictaluridae/anatomía & histología , Canales Iónicos/fisiología , Receptores de Superficie Celular , Transducción de SeñalRESUMEN
Electrophysiological experiments indicate that olfactory receptors of the channel catfish, Ictalurus punctatus, contain different receptor sites for the acidic (A), basic (B), and neutral amino acids; further, at least two partially interacting neutral sites exist, one for the hydrophilic neutral amino acids containing short side chains (SCN), and the second for the hydrophobic amino acids containing long side chains (LCN). The extent of cross-adaptation was determined by comparing the electro-olfactogram (EOG) responses to 20 "test" amino acids during continuous bathing of the olfactory mucosa with water only (control) to those during each of the eight "adapting" amino acid regimes. Both the adapting and test amino acids were adjusted in concentrations to provide approximately equal response magnitudes in the unadapted state. Under all eight adapting regimes, the test EOG responses were reduced from those obtained in the unadapted state, but substantial quantitative differences resulted, depending upon the molecular structure of the adapting stimulus. Analyses of the patterns of EOG responses to the test stimuli identified and characterized the respective "transduction processes," a term used to describe membrane events initiated by a particular subset of amino acid stimuli that are intricately linked to the origin of the olfactory receptor potential. Only when the stimulus compounds interact with different transduction processes are the stimuli assumed to bind to different membrane "sites." Four relatively independent L-alpha-amino acid transduction processes (and thus at least four binding sites) identified in this report include: (a) the A process for aspartic and glutamic acids; (b) the B process for arginine and lysine; (c) the SCN process for glycine, alanine, serine, glutamine, and possibly cysteine; (d) the LCN process for methionine, ethionine, valine, norvaline, leucine, norleucine, glutamic acid-gamma-methyl ester, histidine, phenylalanine, and also possibly cysteine. The specificities of these olfactory transduction processes in the catfish are similar to those for the biochemically determined receptor sites for amino acids in other species of fishes and to amino acid transport specificities in tissues of a variety of organisms.
Asunto(s)
Aminoácidos/metabolismo , Células Receptoras Sensoriales/metabolismo , Olfato/fisiología , Adaptación Fisiológica , Animales , Sitios de Unión , Electrofisiología , Peces , Concentración de Iones de HidrógenoRESUMEN
In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that both electro-olfactogram and integrated neural responses of olfactory receptor cells to complex mixtures consisting of up to 10 different amino acids were predictable with knowledge of (a) the responses to the individual components in the mixture and (b) the relative independence of the respective receptor sites for the component stimuli. All amino acid stimuli used to form the various mixtures were initially adjusted in concentration to provide approximately equal response magnitudes. Olfactory receptor responses to both multimixtures and binary mixtures were recorded. Multimixtures were formed by mixing equal aliquots of 3-10 different amino acids. Binary mixtures were formed by mixing equal aliquots of two equally stimulatory solutions. Solution 1 contained either one to nine different neutral amino acids with long side-chains (LCNs) or one to five different neutral amino acids with short side-chains (SCNs). Solution 2, comprising the binary mixture, consisted of only a single stimulus, either a LCN, SCN, basic, or acidic amino acid. The increasing magnitude of the olfactory receptor responses to mixtures consisting of an increasing number of neutral amino acids indicated that multiple receptor site types with highly overlapping specificities exist to these compounds. For both binary mixtures and multimixtures composed of neutral and basic or neutral and acidic amino acids, the receptor responses were significantly enhanced compared with those mixtures consisting of an equal number of only neutral amino acids. These results demonstrate that receptor sites for the basic and acidic amino acids, respectively, are highly independent of those for the neutral amino acids, and suggest that a mechanism for synergism is the simultaneous activation of relatively independent receptor sites by the components in the mixture. In contrast, there was no evidence for the occurrence of mixture suppression.
Asunto(s)
Aminoácidos/farmacología , Ictaluridae/fisiología , Mucosa Olfatoria/fisiología , Células Receptoras Sensoriales/fisiología , Animales , Interpretación Estadística de Datos , Potenciales de la Membrana/fisiología , Neuronas Aferentes/fisiología , Mucosa Olfatoria/efectos de los fármacosRESUMEN
Odorant receptors activated by amino acids were investigated with patch-clamp techniques in olfactory receptor neurons of the channel catfish, Ictalurus punctatus. The L-isomers of alanine, norvaline, arginine, and glutamate, known to act predominantly on different olfactory receptor sites, activated nondesensitizing inward currents with amplitudes of -2.5 to -280 pA in olfactory neurons voltage-clamped at membrane potentials of -72 or -82 mV. Different amino acids were shown to induce responses in the same sensory neurons; however, the amplitude and the kinetics of the observed whole cell currents differed among the stimuli and may therefore reflect activation of different amino acid receptor types or combinations of receptor types in these cells. Amino acid-induced currents appeared to have diverse voltage dependence and could also be classified according to the amplitude of the spontaneous channel fluctuations underlying the macroscopic currents. A mean single-channel conductance (gamma) of 360 fS was estimated from small noise whole-cell currents evoked by arginine within the same olfactory neuron in which a mean gamma value of 23.6 pS was estimated from 'large noise' response to norvaline. Quiescent olfactory neurons fired bursts of action potentials in response to either amino acid stimulation or application of 8-Br-cyclic GMP (100 microM), and voltage-gated channels underlying generation of action potentials were similar in these neurons. However, in whole-cell voltage-clamp, 8-Br-cyclic GMP evoked large rectangular current pulses, and single-channel conductances of 275, 220, and 110 pS were obtained from the discrete current levels. These results suggest that in addition to the cyclic nucleotide-gated transduction channels, olfactory neurons of the channel catfish possess a variety of odor receptors coupled to different types of transduction channels.
Asunto(s)
Aminoácidos/farmacología , Ictaluridae/metabolismo , Neuronas Aferentes/efectos de los fármacos , Receptores Odorantes/efectos de los fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Electrofisiología , Técnicas In Vitro , Activación del Canal Iónico/efectos de los fármacos , Membranas/efectos de los fármacos , Membranas/metabolismo , Cavidad Nasal/metabolismo , Cavidad Nasal/ultraestructura , Neuronas Aferentes/ultraestructura , Receptores de Aminoácidos/efectos de los fármacos , Receptores de Aminoácidos/metabolismo , Receptores Odorantes/ultraestructura , Transducción de Señal/efectos de los fármacosRESUMEN
In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type.
Asunto(s)
Aminoácidos/farmacología , Bagres/fisiología , Ictaluridae/fisiología , Células Receptoras Sensoriales/efectos de los fármacos , Olfato/efectos de los fármacos , Animales , Electrofisiología , Vías Olfatorias/fisiología , Células Receptoras Sensoriales/fisiología , Olfato/fisiologíaRESUMEN
Correlation of the somatotopic organization of the facial lobe (FL), a primary medullary gustatory nucleus in the channel catfish Ictalurus punctatus, with its lobular substructure was investigated to examine a possible structural basis for the excellent ability of ictalurid catfishes to localize a food source in the environment. The FL in the channel catfish is composed of six longitudinal columns (i.e., lobules) extending rostrocaudally and differing from each other in their length and location within the lobe. Each lobule receives segregated input from discrete portions of the external body surface. The three more medial lobules in the FL receive input (from medial to lateral) from the medial mandibular barbel, the lateral mandibular barbel, and the maxillary barbel, respectively. The proximal-distal axis of each of the barbels is represented in a posteroanterior lobule axis. The largest lobule, the face-flank lobule, is located dorsolaterally in the FL, whereas the anteroposterior body axis is represented in the posteroanterior lobule axis. This indicates that the neural representation of the external body surface of the channel catfish faces caudally in the FL. The two shortest lobules, positioned ventral to the face-flank lobule, receive input from the nasal barbel and the pectoral fin, respectively. The rostrocaudal dimensions of each of the barbel lobules correlate well with the relative lengths of the barbels. Taste-sensitive portions within the three barbel lobules examined were generally confined to the dorsal region, whereas tactile responses were observed throughout the lobules.2+ primarily tactile, zone.
Asunto(s)
Bagres/anatomía & histología , Ictaluridae/anatomía & histología , Bulbo Raquídeo/anatomía & histología , Neuronas/fisiología , Animales , Electrofisiología , Ictaluridae/fisiología , Bulbo Raquídeo/fisiología , Gusto/fisiologíaRESUMEN
To reveal the somatotopical organization of the facial lobe (FL), a primary medullary gustatory nucleus in the sea catfish Arius felis, the central projections of the peripheral rami of the facial nerve innervating taste buds located across the entire body surface and rostral oral regions were traced by means of horseradish peroxidase neurohistochemistry. The maxillary barbel, lateral mandibular barbel, medial mandibular barbel, and trunk-tail branches project to four different longitudinal columns (i.e., lobules) extending rostrocaudally in the FL. The trunk-tail lobule, which is located dorsolateral to the barbel lobules, lies in the anterior two-thirds of the FL. The tail is represented in a more rostral portion of the trunk-tail lobule than the trunk, indicating that the rostrocaudal trunk axis is represented in the trunk-tail lobule in a posteroanterior axis. The pectoral fin branch ends in an intermediate region of the FL, whereas the hyomandibular, ophthalmic, lower lip, upper lip, and palatine branches terminate in discrete regions of the caudal one-third of the FL. These results reveal a sharply defined somatotopical organization of the FL of Arius and support the hypothesis that the number and lengths of the barbel lobules within the FL of catfishes are directly related to the number and relative lengths of the barbels. An additional subcolumn, the intermediate nucleus of the FL (NIF), which develops in the medioventral region of the caudal two-thirds of the FL, receives projections in a diffuse somatotopical fashion from the barbels, lower lip, and palatine branches. Trigeminal fibers of the barbel and lower lip branches project in a somatotopic fashion to the FL. The present findings suggest that the FL of Arius is highly organized somatotopically to detect, by tropotaxis, precise spatial information concerning taste and tactile stimuli in the environment.
Asunto(s)
Bagres/anatomía & histología , Nervio Facial/citología , Ganglios Sensoriales/citología , Bulbo Raquídeo/citología , Animales , Nervio Facial/anatomía & histología , Ganglios Sensoriales/anatomía & histología , Histocitoquímica , Peroxidasa de Rábano Silvestre , Bulbo Raquídeo/anatomía & histología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/citología , Gusto/fisiología , Papilas Gustativas/fisiología , Nervio Vago/citología , Nervio Vago/fisiologíaRESUMEN
Transganglionic transport of horseradish peroxidase was used to trace the pattern of medullary terminations of the glossopharyngeal and vagal nerve complex in the channel catfish, Ictalurus punctatus. The glossopharyngeal root terminates centrally in the anterior end of the vagal lobe except for two fascicles that terminate in separate regions of the nucleus intermedius of the facial lobe. Vagal nerve branches innervating regions of the oropharynx terminate in an overlapping, segmental fashion throughout the ipsilateral vagal lobe and the nucleus intermedius of the vagal lobe. The descending branch of the vagus, innervating the abdominal viscera, terminates in the general visceral nucleus and in the nucleus intermedius of the vagal lobe. In addition, abdominal visceral fibers decussate through the commissural nucleus of Cajal and terminate in the general visceral nucleus of the contralateral side. Efferents included in the oropharyngeal and abdominal branches of the vagus also originate from two morphologically separable populations of motor neurons.
Asunto(s)
Tronco Encefálico/anatomía & histología , Bagres/anatomía & histología , Nervio Glosofaríngeo/anatomía & histología , Ictaluridae/anatomía & histología , Nervio Vago/anatomía & histología , Vías Aferentes/anatomía & histología , Animales , Vías Eferentes/anatomía & histologíaRESUMEN
Vertebrate gustatory systems include a tertiary ascending pathway from a secondary gustatory nucleus in the hindbrain to several forebrain nuclei. This connection is prominent in catfish, corresponding to their highly developed sense of taste. Iontophoretic injections of horseradish peroxidase were used to identify the specific target nuclei of the tertiary gustatory pathway in channel catfish and to characterize those nuclei by their respective connections. Efferents from the secondary gustatory nucleus (nGS) ascend in the tertiary gustatory tract to the caudal inferior lobe, where they terminate caudally in the nucleus lobobulbaris (nLB) and nucleus centralis (nCLI), and rostrally in the nucleus diffusus (nDLI). Secondary projections from the facial lobe (FL) also terminate in the nLB and in the nucleus subglomerulus (nSG). The nLB forms three cell groups (caudal--nLB, rostrolateral--rl nLB, parvicellular--nLBp), which project to the facial lobe, vagal lobe, and telencephalon, respectively. Cells from the nCLI project throughout the caudal inferior lobe and to the acousticolateral torus semicircularis and telencephalon, while the nDLI and nSG have intrinsic connections within the inferior lobe. The lateral thalamic nucleus projects from this region back to the nGS. Through these identified connections several mechanisms for the processing of gustatory information can be proposed. The descending projections from the nLB and nLT could provide feedback to the primary and secondary gustatory nuclei, and could modulate feeding-related motor circuits in the medulla. The connections of nCLI and nLBp with the telencephalon allow for the involvement of gustation in learning processes and other complex behaviors.
Asunto(s)
Diencéfalo/fisiología , Ictaluridae/fisiología , Gusto/fisiología , Vías Aferentes/anatomía & histología , Vías Aferentes/fisiología , Animales , Diencéfalo/anatomía & histología , Histocitoquímica , Peroxidasa de Rábano Silvestre , Hipotálamo/anatomía & histología , Hipotálamo/fisiología , Bulbo Raquídeo/anatomía & histología , Bulbo Raquídeo/fisiología , Puente/anatomía & histología , Puente/fisiología , Coloración y Etiquetado , Núcleos Talámicos/anatomía & histología , Núcleos Talámicos/fisiologíaRESUMEN
Many teleosts possess an enlargement of the ventral diencephalon called the inferior lobe. In ostariophysine species (e.g., carps and catfishes), this region receives ascending fibers from the primary and secondary gustatory centers in the hindbrain. Extracellular unit activity was recorded from identified nuclei in the inferior lobe of the channel catfish to characterize taste and tactile responsiveness from the different nuclei associated with gustatory projections. Taste responses (to amino acids and nucleotides) were recorded from units in the nucleus centralis (nCLI), nucleus lobobulbaris (caudal portion--nLB, rostrolateral portion--rl nLB, and parvicellular portion--nLBp), and lateral thalamic nucleus (nLT), supporting the proposed gustatory role for these nuclei. Tactile responsiveness was distinct between different nuclei in the caudal inferior lobe. Units from the nCLI and nLB had lower spontaneous activity than those from other nuclei, and typically had receptive fields including the whole extraoral body surface, ipsilaterally. Units from the rl nLB and nLBp had receptive fields, often including both oral and extraoral surfaces, bilaterally, but rl nLB receptive fields typically included the whole body, while those from nLBp units were often restricted to the head and mouth. The apparent electrophysiological distinction between these nuclei, combined with their different connectivity patterns, suggest that the gustatory nuclei in the inferior lobe of channel catfish are involved in various different sensory processing mechanisms.
Asunto(s)
Diencéfalo/fisiología , Ictaluridae/fisiología , Neuronas Aferentes/fisiología , Gusto/fisiología , Tacto/fisiología , Vías Aferentes/fisiología , Animales , Diencéfalo/citología , Electrofisiología , Hipotálamo/fisiología , Iontoforesis , Núcleos Talámicos/fisiologíaRESUMEN
Horseradish peroxidase tracing and extracellular electrophysiological recording techniques were employed to delineate prosencephalic connections of the gustatory system in ictalurid catfishes. The isthmic secondary gustatory nucleus projects rostrally to several areas of the ventral diencephalon including the nucleus lobobulbaris and the nucleus lateralis thalami. Injections of HRP in the vicinity of the nucleus lobobulbaris reveal an ascending projection to the telencephalon terminating in the area dorsalis pars medialis (Dm) and the medial region of area dorsalis pars centralis (Dc). Conversely, injections of HRP into the gustatory region of area dorsalis pars medialis label small neurons in the nucleus lobobulbaris. Gustatory neurons in the telencephalon send descending projections via the medial and lateral forebrain bundles to several nuclei in the anterior and ventroposterior diencephalon. The nucleus lateralis thalami, a diencephalic nucleus, receives ascending gustatory projections from the secondary gustatory nucleus but does not project to the telencephalon. Neurons in both the nucleus lateralis thalami and the telencephalic gustatory target exhibit multiple extraoral and oral receptive fields and complex responses to chemical (taste) and tactile stimulation.
Asunto(s)
Bagres/anatomía & histología , Lóbulo Frontal/fisiología , Gusto/fisiología , Vías Aferentes/anatomía & histología , Vías Aferentes/fisiología , Animales , Mapeo Encefálico , Lóbulo Frontal/citología , Peroxidasa de Rábano Silvestre , Estimulación FísicaRESUMEN
Peripheral tolerance, represents an attractive strategy to down-regulate previously activated T cells and suppress an ongoing disease. Herein, immunoglobulins (Igs) were used to deliver self and altered self peptides for efficient peptide presentation without costimulation to test for modulation of experimental allergic encephalomyelitis (EAE). Accordingly, the encephalitogenic proteolipid protein (PLP) sequence 139-151 (referred to as PLP1) and an altered form of PLP1 known as PLP-LR were genetically expressed on Igs and the resulting Ig-PLP1 and Ig-PLP-LR were tested for efficient presentation of the peptides and for amelioration of ongoing EAE. Evidence is presented indicating that Ig-PLP1 as well as Ig-PLP-LR given in saline to mice with ongoing clinical EAE suppresses subsequent relapses. However, aggregation of both chimeras allows crosslinking of Fcgamma receptors (FcgammaRs) and induction of IL-10 production by APCs but does not promote the up-regulation of costimulatory molecules. Consequently, IL-10 displays bystander suppression and synergizes with presentation without costimulation to drive effective modulation of EAE. As Ig-PLP1 is more potent than Ig-PLP-LR in the down-regulation of T cells, we conclude that peptide affinity plays a critical role in this multi-modal approach of T cell modulation.
Asunto(s)
Autoantígenos/metabolismo , Enfermedades Autoinmunes/terapia , Inmunoterapia/métodos , Animales , Células Presentadoras de Antígenos/inmunología , Enfermedades Autoinmunes/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/terapia , Humanos , Inmunoglobulinas/uso terapéutico , Interferón gamma/biosíntesis , Interleucina-10/farmacología , Ratones , Proteína Proteolipídica de la Mielina/inmunología , Proteína Proteolipídica de la Mielina/uso terapéutico , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/uso terapéutico , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Linfocitos T/inmunologíaRESUMEN
Autoimmunity arises when the immune system no longer tolerates self and precipitates lymphocyte reactivity against our own antigens. Although the developing T cell repertoire is constantly purging, self-recognition events do exist when such tight control is evaded and autoreactive lymphocytes escape the thymus (the sites of T cell development) and migrate to the periphery. Upon activation these autoreactive cells may exert aggressive behavior toward one's own tissues and organs leading to autoimmune disease. Multiple sclerosis, Rheumatoid arthritis, and type I diabetes are autoimmune diseases mediated by autoreactive T cells. A logical approach to prevent such autoimmunity would be to reprogram those lymphocytes to tolerate the self antigen. Injection of antigen at the neonatal stage promotes a state of tolerance such that successive encounter with antigen does not precipitate aggressive reactions. The mechanism underlying neonatal tolerance involves priming of T cells whose effector functions do not cause inflammatory reactions upon recognition of antigen but rather induce protective immunity. This form of tolerant immunity provides an attractive strategy for vaccination against autoimmunity. Herein, it is shown that neonatal exposure to a self-peptide-immunoglobulin chimera drives a tolerant immunity toward the self-peptide and protects against the autoimmune disease, experimental allergic encephalomyelitis.
Asunto(s)
Animales Recién Nacidos/inmunología , Autoinmunidad/inmunología , Tolerancia Inmunológica/inmunología , Recién Nacido/inmunología , Vacunación , Animales , Presentación de Antígeno/inmunología , Humanos , Inmunoglobulinas/inmunología , Péptidos/inmunologíaRESUMEN
The ultrastructure of the olfactory epithelium in intact, axotomized, and bulbectomized goldfish was studied by scanning and transmission electron microscopy. A total of 58 adult goldfish of various survival times were examined to determine whether the different types of surgery--either olfactory nerve transection or bulbectomy--yielded differences in the extent or time course of cellular degeneration and renewal. Control animals were also examined in detail to elucidate previous controversial findings concerning the types of olfactory receptor neurons present in goldfish. We found that the intact olfactory epithelium of unoperated control goldfish contains the previously observed ciliated and microvillous receptor neurons, and the crypt cell, a cell type not yet seen in the goldfish but recently reported in other species of teleosts. Following either olfactory nerve transection or bulbectomy, the olfactory receptor neurons showed similar signs of degeneration and subsequent cell death, but, surprisingly, the thickness of the olfactory epithelium did not change significantly with either treatment. The time course of receptor cell renewal was different in axotomized and bulbectomized goldfish. In axotomized goldfish, the amount of receptor cells decreased continuously until 8-13 days after surgery, followed by rapid cell renewal. For bulbectomized goldfish, cell replacement began almost immediately after surgery, with degeneration and cell renewal occurring simultaneously. Six weeks after bulbectomy, cell death and cell proliferation reached a "steady state," and the epithelia did not further improve.
Asunto(s)
Carpa Dorada/anatomía & histología , Bulbo Olfatorio/ultraestructura , Animales , Axotomía , Epitelio/fisiología , Epitelio/ultraestructura , Microscopía Electrónica/métodos , Bulbo Olfatorio/fisiología , Bulbo Olfatorio/cirugía , RegeneraciónRESUMEN
BACKGROUND: Little is known about physicians' perceptions of the influence of culture on the health care of children with chronic and disabling conditions. OBJECTIVE: To identify physicians' perceptions of the impact of the family's ethnocultural background on the health care of school-aged children with chronic conditions and recommendations for improving care. DESIGN: Qualitative study in 2 midwestern metropolitan areas. SETTING: General community. PARTICIPANTS: Convenience sample of 52 physicians nominated by 60 African American, Hispanic, and European American families of school-aged children with chronic conditions. METHODS: In-depth interviews were conducted with the physicians. Content analytic techniques were used to analyze the data. RESULTS: In 44% of the responses, the physicians reported that ethnocultural background did not influence the care the child received, noting that comparable care was provided to all of their patients. In 14% of the responses, the effect was unknown. The overall effect was negative in 26% of the responses and positive in 16%. Physicians' recommendations focused on 4 topics: improving the training and education of health care professionals and families; ensuring good communication between the child, family, and health care professionals; supporting families; and improving the access and provision of services for children from diverse cultural backgrounds. CONCLUSION: Although the majority of participants reported that ethnocultural background did not affect the care the child received from the health care system, physicians' recommendations reflected awareness of the influence of culture on the care of children with chronic conditions and the need for further training on this issue.
Asunto(s)
Servicios de Salud del Niño , Enfermedad Crónica , Cultura , Personas con Discapacidad , Calidad de la Atención de Salud , Actitud del Personal de Salud , Chicago , Niño , Preescolar , Barreras de Comunicación , Necesidades y Demandas de Servicios de Salud , Humanos , Minnesota , Pediatría/educación , Relaciones Profesional-Familia , Apoyo SocialAsunto(s)
Neoplasias de la Mama/química , Núcleo Celular/química , Proteínas de Neoplasias/análisis , Neoplasias Ováricas/química , Factores de Transcripción/análisis , Secuencia de Aminoácidos , Proteína BRCA1 , Neoplasias de la Mama/ultraestructura , Línea Celular , Citoplasma/química , Femenino , Técnica del Anticuerpo Fluorescente , Técnicas de Preparación Histocitológica , Humanos , Técnicas para Inmunoenzimas , Datos de Secuencia Molecular , Proteínas de Neoplasias/inmunología , Neoplasias Ováricas/ultraestructura , Factores de Transcripción/inmunología , Células Tumorales CultivadasRESUMEN
Neurons in the intermediate nucleus of the facial lobe (nIF) in the channel catfish that respond to tactile stimulation of oral and/or extra-oral epithelia are somatotopically arranged. Neurons in rostrodorsal portions of the nIF responded to tactile stimulation or deflection of the ipsilateral barbels, whereas neurons arranged in a dorsoventral direction in caudoventral regions of the nIF had receptive fields on the ipsilateral lips and the oral cavity, respectively. Suppression of neuronal activity in response to tactile stimulation of the external skin and/or the oral cavity was indicated for some units. Taste responses were not observed.
Asunto(s)
Bagres/fisiología , Ictaluridae/fisiología , Mecanorreceptores/fisiología , Bulbo Raquídeo/fisiología , Boca/inervación , Tacto/fisiología , Potenciales de Acción , Vías Aferentes/fisiología , Animales , Boca/fisiología , Estimulación FísicaRESUMEN
Neural responses in the facial lobe of th channel catfish to chemical and mechanical stimulation of the external skin surface were studied electrophysiologically. Taste and tactile neurons in the lobe were organized in a somatotopic manner, which confirms the anatomical reports of the facial lobe in the bullhead catfish, but is markedly different from that of the Cyprinidae. The taste neurons were arranged generally in the more dorsal regions of the tactile sensitive areas and responded with highest frequency to L-alanine or L-arginine HCI among several amino acids tested. The mechanically responsive neurons in the deeper layer of the antero-medial portion of the lobe, possibly corresponding to the intermediate nucleus of the facial lobe, had large receptive fields ranging from 100 mm to the whole body surface; in addition, some of these neurons showed lateral inhibition. The present study revealed that the facial lobe of the channel catfish is a center not only for gustatory input, but also for tactile information.
Asunto(s)
Bulbo Raquídeo/fisiología , Gusto/fisiología , Tacto/fisiología , Animales , Potenciales Evocados Somatosensoriales , Nervio Facial/fisiología , Peces , Mecanorreceptores/fisiología , Fibras Nerviosas/fisiología , Neuronas/fisiología , Piel/inervación , Papilas Gustativas/fisiologíaRESUMEN
Neurons within the superior secondary gustatory nucleus (nGS) of the channel catfish were examined electrophysiologically for responses to mechanical and chemical stimulation of neural peripheral receptive fields (RFs). Of the 28 single units sampled, 18 had mechanosensory RFs on the extraoral epithelium, two had RFs within the oropharyngeal cavity, and eight had RFs that included both oral and extraoral surfaces. RF sizes varied from approximately 2 cm2 on the ipsilateral lips and barbels to the whole body surface, bilaterally. No obvious correlation existed between RF pattern and recording location within the nGS. Eight of the mechanosensory nGS units also responded to amino acid taste stimuli with thresholds from micromolar to millimolar concentrations. The convergence of oral and extraoral information within the nGS determined electrophysiologically was corroborated anatomically by HRP labeling experiments. Restricted HRP injections into each of the primary gustatory nuclei of the medulla, the vagal (VL) and facial (FL) lobes, labeled fibers that appeared to terminate diffusely throughout the nGS, and injections into different portions of the nGS retrogradely labeled cells in both the FL and VL. The present electrophysiological and neuroanatomical data distinguish the convergent gustatory representation within the nGS of the catfish from the highly specific somatotopic and viscerotopic sensory maps previously identified in the FL and VL, respectively.