Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin.
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PMID:Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas. 748 1

Information concerning the rate of bladder filling is determined by receptors in the bladder wall and conveyed via afferent fibers in the pelvic nerve to sensory neurons in the lumbosacral cord. It was assumed that this information is relayed from the lumbosacral cord to a medial cell group in the dorsolateral pontine tegmentum, called the M-region, the pontine micturition center, or Barrington's nucleus. The M-region, in turn, projects via long descending pathways to the sacral parasympathetic motoneurons. In the present electron microscopic study, it was investigated in cats whether monosynaptic projections from lumbosacral neurons to the M-region indeed exist. Wheat-germ agglutinin-horseradish peroxidase injections were made into the lumbosacral cord. Many retrogradely labeled dendrites and somata were found in the M-region, but no labeled terminals were found on retrogradely labeled dendrites or somata. Only a small number of anterogradely labeled terminals, which were filled with mainly round vesicles, contacted unlabeled dendrites in the M-region. In contrast, many more anterogradely labeled terminals, which were filled with mainly round and, to a limited extent, dense core vesicles and with asymmetrical synapses, were found on dendrites in the lateral part of the periaqueductal gray (PAG). Previously (Blok and Holstege [1994] Neurosci. Lett. 166:93-96), it was demonstrated that the lateral part of the PAG contains neurons projecting to the M-region. A concept for the central organization of the micturition reflex is presented in which ascending projections from the lumbosacral cord convey information on bladder filling to the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ultrastructural evidence for a paucity of projections from the lumbosacral cord to the pontine micturition center or M-region in the cat: a new concept for the organization of the micturition reflex with the periaqueductal gray as central relay. 749 30

The synaptic circuitry of the intrinsic GABAergic system of the central extended amygdala (CEA) in relation to efferent neurons and cortical afferents was examined in the present study. Neurons in the CEA projecting to the dorsal vagal complex and the parabrachial complex were identified by the retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Postembedding GABA-immunocytochemistry revealed that GABA-immunoreactive (GABA-IR) terminals formed largely symmetrical synaptic contacts with the perikarya and proximal dendritic processes of almost all WGA-HRP-labeled neurons in the CEA. To determine the relationship between cortical afferents and CEA GABAergic neurons, WGA-HRP was used to anterogradely label afferents from the insular cortex in combination with postembedding immunogold detection of GABA. Cortical afferents formed asymmetrical synaptic contacts predominantly on small dendrites and dendritic spines. Many of the dendrites postsynaptic to cortical terminals in the central nucleus were immunoreactive for GABA although only relatively few spines were GABA-IR. Combining pre-embedding GAD-immunocytochemistry with cortical lesions resulted in approximately 40% of degenerating terminals of insular cortical origin in the central nucleus in contact with small, GAD-IR dendrites and spines. The present results demonstrate that the neurons providing the major CEA outputs to the brainstem receive an extensive GABAergic innervation, strongly supporting our proposal that CEA efferent neurons are under strong tonic inhibition by intrinsic GABAergic neurons. Further, our finding that the major cortical input to the central nucleus preferentially innervates intrinsic GABAergic neurons suggests that these neurons in the CEA may serve as an interface between the principal inputs and outputs of this forebrain region.
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PMID:Evidence for a GABAergic interface between cortical afferents and brainstem projection neurons in the rat central extended amygdala. 751 19

The organization of limbic cortical afferents to the thalamic reticular nucleus (TRN) is described. Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), biocytin, neurobiotin, or fluorescent dextrans was delivered into the rat cingulate, retrosplenial, and, for comparison, somatosensory cortices. In other species a slab-like arrangement of cortical terminals has been described for sensory TRN sectors. Here this is seen in the rat somatosensory sector. Terminals from limbic cortices did not cluster into slabs but were found to fill the entire thickness of distinct rostral TRN regions. The cingulate and retrosplenial recipient TRN regions overlap, as do the projections from these cortical areas to anterior thalamic nuclei. Retrosplenial fibres contacted the dorsal and rostral TRN, which is known to be connected to the retrosplenial-recipient anteroventral, anterodorsal, and laterodorsal thalamic nuclei. Cingulate terminals occupied more ventral regions of the rostral TRN. This area is connected to thalamic nuclei also innervated by the cingulate cortex: the mediodorsal and anteromedial nuclei. A loose, but clear, topography could be defined for the cingulate-reticular pathway: rostrocaudal and mediolateral directions in the cortex are represented by ventrodorsal and rostrocaudal directions in the TRN, respectively. This organization of limbic corticoreticular pathway corresponds to the arrangement of limbic corticothalamic connections. The ultrastructure of the limbic cortical axon terminals was similar to that of the cortical boutons (D-type) described previously. The labelled terminals formed asymmetrical synapses onto dendritic profiles of reticular neurons. These findings, together with data in the literature, show significant morphological and connectional differences within the TRN that imply functional heterogeneities.
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PMID:Organization of cortical afferents to the rostral, limbic sector of the rat thalamic reticular nucleus. 751 2

In order to determine whether neurones in the parvicellular reticular formation are in direct synaptic contact with motoneurones innervating facial muscles, a combined retrograde and anterograde transport study was carried out in the rat. Animals received injections of the retrograde tracer cholera toxin B conjugated to horseradish peroxidase into facial muscles and of the anterograde tracer biocytin into the parvicellular reticular formation. The facial motor nucleus was then examined for anterograde and retrograde labelling in the light and electron microscopes. Retrogradely labelled neurones were found in the facial motor nucleus with a distribution that was dependent on the muscles injected. Terminals anterogradely labelled with biocytin from the parvicellular reticular formation was observed in the motor nucleus amongst the retrogradely labelled neurones. At the electron microscope, the retrogradely labelled cells were found to receive input from unlabelled terminals and from terminals that were anterogradely labelled from the injections of biocytin in the parvicellular reticular formation. The labelled terminals were 1-2 microns in diameter at the active zone and packed with spherical vesicles. They formed both symmetrical and asymmetrical synapses with their labelled or unlabelled targets. It is concluded that neurones in the parvicellular reticular formation form direct synaptic contact with motoneurones of facial muscles. This may represent a pathway by which the basal ganglia can directly influence orofacial movement, as the substantia nigra is known to project to that part of the reticular formation.
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PMID:Monosynaptic innervation of facial motoneurones by neurones of the parvicellular reticular formation. 753 50

The nucleus tractus solitarii, the first central relay for gustatory and a variety of visceral afferents, is also an integrative center for numerous functions. Its interstitial subdivision is involved in swallowing and respiratory reflexes. The ultrastructural characteristics of this subdivision and of its laryngeal afferents were investigated in adult rat by a serial-section study and by application of wheat germ agglutinin-horseradish peroxidase conjugate to the peripheral afferent fibers. The interstitial subnucleus contained scattered small neuronal cell bodies with such ultrastructural features as a large nucleus with deep indentations and an organelle-poor cytoplasm. On the basis of their size and vesicular content, the axon terminals were classified into three categories. Group I and group II terminals were small or large, respectively, and contained mainly small, round, and clear synaptic vesicles. Group III terminals were also small but contained small, pleomorphic, and clear vesicles. Axodendritic synapses were the most numerous. They were either asymmetrical, comprised of group I and II terminals, or symmetrical, comprised of group III terminals. More than 50% were part of complex synaptic arrangements in the form of rosettes or glomeruli. Axosomatic contacts involved both group I and group III terminals and were always symmetrical. A high frequency of axoaxonic synapses was found. They were symmetrical, comprised of group III terminals on group I or II terminals. Different types of symmetrical synaptic contacts made by dendrites were also found. This study indicates also that the ipsilateral interstitial subdivision constitutes the preferential site of termination for superior laryngeal afferents. The labeled axon terminals belonged exclusively to groups I and II and were involved in both axodendritic and axoaxonic synapses. Some of the axodendritic synapses were part of rosettes or glomeruli. All these synaptic arrangements may be considered a morphological substrate for important processing of afferent information in the nucleus tractus solitarii. They may account for some of the integrative functions of the interstitial subnucleus such as physiological processes triggered from the superior laryngeal nerve.
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PMID:Synaptic organization of the interstitial subdivision of the nucleus tractus solitarii and of its laryngeal afferents in the rat. 754 10

A combined anterograde axonal degeneration and Golgi electron microscopic (Golgi-EM) study was undertaken to identify thalamocortical synaptic connections between axon terminals from the mediodorsal thalamic nucleus (MD) and pyramidal cells in layers III and V of the agranular prelimbic cortex in the rat. The morphological characteristics of thalamocortical synapses from MD were also examined by labeling axon terminals with anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). WGA-HRP labeled axon terminals from MD to the prelimbic cortex were small in size (0.5-1 microns in diameter), contained round synaptic vesicles, and formed axospinous synapses with asymmetrical membrane thickenings. With Golgi-EM methods, gold-toned apical dendrites in layer III were analyzed by reconstruction of serial ultrathin sections. Following lesions in the thalamus, degenerating thalamocortical axon terminals formed asymmetrical contacts exclusively on dendritic spines of the identified apical dendrites. More thalamocortical synapses were found on apical dendrites of layer V pyramidal cells than on apical dendrites of layer III pyramidal cells. In addition to thalamocortical synapses, a very few unlabeled symmetrical synapses were found on apical dendrites and somata of pyramidal cells, but they were not quantified and their sources are unknown.
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PMID:Thalamocortical synapses between axons from the mediodorsal thalamic nucleus and pyramidal cells in the prelimbic cortex of the rat. 754 20

The present study examined GABA immunoreactivity within the retinopetal nucleus isthmo-opticus (NIO) of the pigeon centrifugal visual system (CVS) using light- (immunohistofluorescence, peroxidase anti-peroxidase: PAP) and electron- (postembedding GABA immunogold) microscopic techniques. In some double-labeling experiments, the retrograde transport of the fluorescent dye rhodamine beta-isothiocyanate (RITC) after its intraocular injection was combined with GABA immunohistofluorescence. GABA-immunoreactive (-ir) somata were demonstrated within the neuropilar zone of the NIO adjacent to the centrifugal cell laminae whereas the centrifugal neurons were always immunonegative. A quantitative ultrastructural analysis was performed which distinguished five categories of axon terminal profiles (P1-5) on the basis of various cytological criteria: type of synaptic contact (symmetrical or asymmetrical); shape, size, and density of synaptic vesicles as well as the immunolabeling (positive or negative), size of profile and appearance of hyaloplasm. Numerous GABA-ir afferents to centrifugal neurons via axon terminal types P2a, P2c, and P3 were observed which comprised 47.1% of the total input. Moreover, the data suggest that some of the P2a terminals, which make up 26.4% of the input, stem from the intrinsic GABA-ir interneurons, whereas the latter receive P1, P3, but also P2 terminal input, indicating that interneurons may contact other interneurons via type P2a axon terminals. The results also suggest that the GABA-ir P3 or the immunonegative P1b and P5 axon terminals are of extrinsic origin arising from cells in the optic tectum whereas the P2c and P4 axon terminals are associated with extra-tectal input to the NIO. The GABAergic innervation of centrifugal neurons within the NIO may be the basis for the demonstrated facilitatory effect of the centrifugal output upon ganglion cell responses. This is relevant to hypotheses regarding CVS involvement in attentional mechanisms through selective enhancement of retinal sensitivity depending on the location of meaningful or novel stimuli.
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PMID:GABA immunoreactivity in the nucleus isthmo-opticus of the centrifugal visual system in the pigeon: a light and electron microscopic study. 754 6

We addressed the question whether the projection neurons of the olfactory bulb, i.e. the mitral and tufted cells, are immunoreactive for the calcium-binding protein, calretinin. The following approaches were adopted: (1) light and electron microscopic calretinin-immunocytochemistry; (2) neuroanatomical tracing combined with calretinin-immunocytochemistry according to double-peroxidase and double-fluorescence protocols; (3) unilateral lesion of the olfactory bulb combined with calretinin-immunocytochemistry. The experiments were carried out in rats. Immunostaining of brain sections revealed weakly calretinin-immunopositive mitral cell bodies. Tufted cells were immunonegative. In contrast, fibers in the lateral olfactory tract were strongly immunopositive. Dense immunostaining was also present in a superficial band in layer I of the olfactory tubercle, piriform cortex, periamygdaloid cortex, and in the lateral entorhinal cortex. In electron microscopic preparations of these target areas we observed immunoreaction product in axons and axon terminals. The latter invariably formed asymmetrical synapses, mostly with dendritic spines. Injections of the neuroanatomical tracer biotinylated dextran amine (BDA) into the olfactory bulb produced labeled fibers which remained completely restricted to the superficial, calretinin-immunopositive band in layer I in the above-mentioned cortical forebrain areas. We noted colocalization of transported BDA and calretinin-immunoreactivity in mitral cells, in fibers in the lateral olfactory tract and in fibers in the piriform cortex. Olfactory bulb lesions produced depletion of calretinin-immunoreactivity in the lateral olfactory tract and the superficial band in the olfactory cortex-related areas. Together these data firmly indicate that mitral cells and their axons are calretinin-immunoreactive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calretinin-immunoreactivity in mitral cells of the rat olfactory bulb. 755 32

The modulatory actions of dopamine on the flow of cortical information through the basal ganglia are mediated mainly through two subtypes of receptors, the D1 and D2 receptors. In order to examine the precise cellular and subcellular location of these receptors, immunocytochemistry using subtype specific antibodies was performed on sections of rat basal ganglia at both the light and electron microscopic levels. Both peroxidase and pre-embedding immunogold methods were utilized. Immunoreactivity for both D1 and D2 receptors was most abundant in the neostriatum where it was mainly contained within spiny dendrites and in perikarya. Although some of the immunoreactive perikarya had characteristics of interneurons, most were identified as medium-sized spiny neurons. Immunoreactivity for D1 receptor but not D2 receptor was associated with the axons of the striatonigral pathway and axons and terminals in the substantia nigra pars reticulata and the entopeduncular nucleus. In contrast, D2 immunoreactivity but not D1 immunoreactivity was present in the dopaminergic neurons in the substantia nigra pars compacta and ventral pars reticulata. In the globus pallidus, little immunoreactivity for either D1 or D2 receptor was detected. At the subcellular level, D1 and D2 receptor immunoreactivity was found to be mainly associated with the internal surface of cell membranes. In dendrites and spines immunoreactivity was seen in contact with the membranes postsynaptic to terminals forming symmetrical synapses and less commonly, asymmetrical synapses. The morphological features and membrane specializations of the terminals forming symmetrical synapses are similar to those of dopaminergic terminals previously identified by immunocytochemistry for tyrosine hydroxylase. In addition to immunoreactivity associated with synapses, a high proportion of the immunoreactivity was also on membranes at non-synaptic sites. It is concluded that dopamine receptor immunoreactivity is mainly associated with spiny output neurons of the neostriatum and that there is a selective association of D1 receptors with the so-called direct pathway of information flow through the basal ganglia, i.e. the striatoentopeduncular and striatonigral pathways. Although there is an association of receptor immunoreactivity with afferent synaptic inputs a high proportion is located at extrasynaptic sites.
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PMID:Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy. 760 71


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