Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immunohistochemical study was done for the presence of tyrosine hydroxylase (noradrenergic innervation), neuron-specific protein PGP9.5, and anterior pituitary hormones (beta-subunit of follicle-stimulating hormone, growth hormone, beta-subunit of luteinizing hormone, prolactin, and beta-subunit of thyroid-stimulating hormone) in cultured thymic fragments before and after transplantation in congenitally athymic and euthymic rats. The cultured thymic fragments consisted of epithelial cells and were depleted of lymphocytes. After implantation in syngeneic and allogeneic athymic recipients and in syngeneic euthymic recipients, a recovery of the original architecture was found within 6 weeks; rejection occurred within 3 weeks for allogeneic transplantation in euthymic rats. During culture nerve-like profiles almost disappeared from the tissue, and reappeared simultaneously with the influx of host-derived cells and the restoration of the original thymic architecture. A high immunoreactivity for hormones and PGP9.5 was found in epithelial cells after culture and in the first phase after transplantation. These epithelial cells may represent precursor-epithelial cells, based on their unusual ultrastructure and combined expression of markers that in the normal thymus occur only on subcapsular/medullary epithelium or on cortex epithelium. These data indicate a potential role of the neuroendocrine function of the thymus during restoration of the thymus architecture starting from precursor-like epithelial cells.
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PMID:The neuro-endocrine component of the rat thymus: studies on cultured thymic fragments before and after transplantation in congenitally athymic and euthymic rats. 809 23

This light-microscopic (LM) immunohistochemical study has evaluated the presence and distribution of the pan-neural and neuroendocrine marker protein gene product (PGP) 9.5 in pinealocytes and nerve fibres of guinea-pig pineal gland. The pattern of PGP 9.5-immunoreactive (ir) nerve fibres has been compared with that of fibres staining for tyrosine hydroxylase (TH) or neuropeptide Y (NPY). The vast majority of pinealocytes stained for PGP 9.5, although with variable intensity. PGP 9.5 immunoreactivity was localized in pinealocytic cell bodies and processes. Double-immunofluorescence revealed that PGP 9.5 immunoreactivity was absent from glial cells identified with a monoclonal antibody against glial fibrillary acidic protein (GFAP). PGP 9.5 immunoreactivity was also present in a large number of nerve fibres and varicosities distributed throughout the pineal gland. The number of TH-ir and NPY-ir nerve fibres was lower compared with those containing PGP 9.5 immunoreactivity. All fibres staining for NPY also stained for TH. NPY-ir nerve fibres were found to be much more numerous than previously reported for this species. The double-immunofluorescence analysis indicated that almost all TH-ir nerve fibres of the pineal gland contained PGP 9.5 immunoreactivity. However, few PGP 9.5-ir nerve fibres, located in the periphery and the central part of the gland, were TH-negative. A large number of PGP 9.5-ir fibres was concentrated in the pineal stalk. In contrast, TH-ir and NPY-ir nerve fibres were rare in this part of the pineal gland. Our data provide evidence that immunohistochemistry for PGP 9.5 may be a useful tool further to differentiate central and peripheral origins of pineal innervation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein gene product (PGP) 9.5 immunoreactivity in nerve fibres and pinealocytes of guinea-pig pineal gland: interrelationship with tyrosine- hydroxylase- and neuropeptide-Y-immunoreactive nerve fibres. 809 36

Serial endomyocardial biopsies from 5 patients during the first 3 months after heart transplantation were studied by immunohistochemistry for the neural markers neurofilament 200 kD, neuron-specific protein 9.5 (PGP9.5), S100 (Schwann cell marker), and tyrosine hydroxylase (TH). In normal endomyocardium, nerves immunoreactive for neurofilament 200 kD and PGP9.5 occurred in the interstitium around blood vessels, in close contact with myocyte fibrils. Immunoreactive fibers identified for S100 and TH were also present. In biopsies taken after transplantation, the basic nerve structure in neurofilament labeling was intact. There was a disappearance of immunolabeling for PGP9.5, S100, and TH during the first month after transplantation. Immunoreactivity reappeared during the second month, at first in the interstitium around blood vessels. This was observed for PGP9.5 and TH between 4 and 6 weeks after transplantation, and for S100 (in two of five patients) starting after 6 weeks. There was no apparent relation between reappearance and occurrence of rejection.
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PMID:Innervation of the endomyocardium in the first period after heart transplantation. 810 2

Quantitative measurements of relative nerve density were achieved using computer-assisted image analysis of immunohistochemically and histochemically defined nerves in the conduction system of the guinea pig heart. All regions of the conduction system possessed a similar density of nerve fibres and fascicles displaying immunoreactivity for the general neuronal marker protein gene product 9.5 (PGP 9.5), and this was 3 to 4-fold higher than in the adjacent myocardium. Acetylcholinesterase (AChE) positive and tyrosine hydroxylase (TH)-immunoreactive nerves were the main subtypes identified in the sinus and atrioventricular nodes, representing 40-45% of the stained area occupied by PGP 9.5-immunoreactive nerves. AChE-positive nerves were the dominant subtype identified in the left and right bundle branches, but were equal in proportion to TH-immunoreactive nerves in the penetrating bundle. Neuropeptide Y-immunoreactive nerves represented the main peptide-containing subpopulation in the nodal tissues, displaying a similar pattern of distribution and relative density to those nerves demonstrating TH immunoreactivity. Substance P and calcitonin gene-related polypeptide immunoreactive nerves were present throughout the conduction system and represented the main peptide-containing subpopulation in the ventricular conduction tissues. Nerve fibres showing immunoreactivity for either somatostatin or vasoactive intestinal polypeptide exhibited distinct patterns of distribution and comprised a relatively minor component of the innervation. The innervation of the guinea pig conduction tissues thus exhibits a uniform distribution and it comprises putative parasympathetic nerves and intrinsic neurons (AChE positive), sympathetic efferent nerves (NPY and TH-immunoreactive nerves) as well as other peptide-containing nerves, some of which (substance P and calcitonin gene-related polypeptide) are considered to represent afferent nerves. The distribution and density of nerve subpopulations in the guinea pig conduction system differ from those observed in the human conduction system, which suggests that the guinea pig may be an inappropriate model for comparative functional studies.
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PMID:A quantitative study of nerve distribution in the conduction system of the guinea pig heart. 862 40

The POU family transcription factor Oct-2 was originally identified in B lymphocytes but has been shown to be expressed in neuronal cells, although it is absent in most other cell types. Cotransfection of Oct-2 expression vectors into nonneuronal cells with a tyrosine hydroxylase promoter/reporter plasmid suggests that Oct-2 can repress this promoter in this artificial situation. Here we report that reduction of endogenous Oct-2 levels in a neuronal cell line by an antisense approach results in an increase in endogenous tyrosine hydroxylase levels. In contrast, the level of the neuronal marker protein PGP9.5 remains unchanged in the antisense lines whereas that of the neuronal nitric oxide synthase decreases. Hence, the tyrosine hydroxylase gene is a natural target for repression by Oct-2 in neuronal cells. The significance of this effect is discussed in terms of the processes that regulate tyrosine hydroxylase gene expression and the role of Oct-2 in neuronal cells.
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PMID:Direct evidence that the POU family transcription factor Oct-2 represses the cellular tyrosine hydroxylase gene in neuronal cells. 867 99

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.
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PMID:Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis). 869 72

Contact with sweat gland acini causes sympathetic neurons to switch from a catecholaminergic to a cholinergic phenotype during development and following experimental manipulations. Substantial reductions of cholinergic innervation have been shown in the sweat glands of ageing rats and humans. Using in oculo transplantation, we have now studied whether sweat gland target tissues retain the capacity to regulate changes in the phenotype of sympathetic neurons observed in maturity and old age, including a switch from catecholaminergic to cholinergic characters. Markers have been used which indicate changes in nerve fibre morphology (the pan-neuronal marker, PGP9.5) as well as neurotransmitter expression (acetylcholinesterase (AChE), vasocative intestinal polypeptide (VIP) and tyrosine hydroxylase (TH)). Sweat glands from young and old donor rats became reinnervated by an organotypic pattern of cholinergic host nerves. Surgical sympathectomy demonstrated that these cholinergic nerve fibres originate from sympathetic neurons of the host superior cervical ganglion (SCG). Retrograde tracing combined with staining for VIP (a marker associated with cholinergic phenotype in neurons supplying sweat glands) showed that SCG neurons projecting to irises with sweat gland implants may be induced to express VIP. We hypothesise that these neurons have been switched from their normal catecholaminergic phenotype to a cholinergic one by contact with the sweat gland implants. Transplants from old donors attracted a density of reinnervation by young host nerves which was appropriate to the age of the donor, thus old sweat glands received a significantly reduced density of innervation compared to young glands. Despite the reduced density of innervation, there was no obvious difference in the ability of young and old implants to induce the switch to a cholinergic phenotype, suggesting that different mechanisms regulate nerve growth and neurotransmitter phenotype.
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PMID:Transplanted sweat glands from mature and aged donors determine cholinergic phenotype and altered density of host sympathetic nerves. 891 74

Long-term (2-12 weeks) cultures of adult guinea-pig ventricular myocytes, cocultured with neurons derived from stellate or intrinsic cardiac ganglia, retain their functional properties (Horackova et al., 1993, 1994, 1995). The present study was designed to investigate the morphological and immunochemical properties of such neurons and their associated cardiomyocytes. Cultured myocytes studied by means of phalloidin-rhodamine (for F-actin) and an antibody raised against myomes revealed parallel myofibrils with striations typical of rod-shaped cardiomyocytes, even while myocytes changed from cylindrical to flattened form as they established intercellular contacts. Microtubular networks, identified by alpha-tubulin DM1A antibody, were arrayed longitudinally in myofibrils, being especially prominent during the formation of intercellular contacts between myocytes. Histochemically identified adult peripheral autonomic neurons cultured alone or with myocytes displayed a variety of shapes. alpha-Tubulin staining was associated with the somata and neurites of various-shaped neurons whether cultured alone or with myocytes. Cultured neurons derived from stellate and intrinsic cardiac ganglia also exhibited staining for the general neuronal marker PGP 9.5 (protein gene product 9.5), and for specific markers of the following neurochemicals: tyrosine hydroxylase, acetylcholinesterase, choline acetyltransferase, neuropeptide Y, vasoactive intestinal peptide, calcitonin gene-related peptide, bradykinin, oxytocin, and NADPH-diaphorase. These data indicate that: (a) adult ventricular myocytes cocultured with intrathoracic neurons retain the structural properties of adult myocytes found in vivo; (b) intrinsic cardiac and extrinsic intrathoracic neurons cultured alone or with cardiomyocytes display morphological characteristics similar to those of neurons studied in situ; (c) intrinsic cardiac and intrathoracic extracardiac neurons cultured alone or with cardiomyocytes display a variety of morphologies (unipolar, bipolar, and multipolar), larger and more multipolar neurons being present in cultures derived from stellate versus intrinsic cardiac ganglia; (d) such cultured neurons are associated with a number of neurochemicals, more than one chemical being associated with each neuron. This model presents an excellent opportunity to study the morphology of individual peripheral extracardiac and intracardiac neurons as well as their potential to produce various neurochemicals that are known to be involved in the neuromodulation of cardiomyocyte function.
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PMID:Morphological and immunohistochemical properties of primary long-term cultures of adult guinea-pig ventricular cardiomyocytes with peripheral cardiac neurons. 876 Aug 56

In the present study the topographical distribution of the intrinsic nerve plexuses of the basal cerebral arteries in humans was quantified and the relation between vessel diameter and nerve density was investigated. Whole-mount preparations of various segments of the basal cerebral arteries from middle-aged patients were stained for protein gene product (PGP) 9.5. The deep nerve plexuses, located at the adventitial-medial border, were quantified by image analysis. Confocal scanning laser microscopy was used to study nerve plexuses throughout the adventitia. Transverse cryostat sections were stained for PGP 9.5, tyrosine hydroxylase and neurofilament, and quantified. The results showed a three-layered configuration of the adventitial nerves. Measurements on whole-mounts demonstrated that nerve densities were highest in the posterior communicating artery (PCom), and next highest in the proximal parts of the posterior cerebral artery (PCA) and anterior choroidal artery. There appeared to be no clear relation between nerve density and vessel diameter. The measurements on sections confirmed the high nerve densities in the PCom and PCA. Tyrosine hydroxylase- and neurofilament-immunoreactivities appeared to demonstrate separate subpopulations of the overall nerve plexuses, representing sympathetic and, possibly, sensory fibers, respectively. Densities of both subgroups generally followed those of PGP 9.5-immunoreactive nerves. Transmission electron microscopy suggested motor function of the deep nerve plexuses. The results indicate a stronger neuronal influence on this part of the cerebral circulation than hitherto reported. It is concluded that human basal cerebral arteries display a topographical distribution of deep perivascular nerves, and that nerve density is determined by locality rather than by vascular diameter.
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PMID:Perivascular nerves of the human basal cerebral arteries: I. Topographical distribution. 878 49

The peptidergic innervation of the guinea-pig basilar artery and the posterior, middle and anterior cerebral arteries were studied by means of immunohistochemical and image analysis techniques using whole mount preparations. An in vitro pharmacological study was performed to correlate the distribution of peptide-containing nerves and the action of neuropeptides on vessel segments from the same vascular regions. The overall distribution of perivascular nerve fibres was demonstrated using an antiserum to the general neuronal marker protein gene product 9.5 (PGP 9.5) and the percentage immunostained area of total vessel wall area occupied by PGP-containing nerves, in each of the basilar, posterior and middle cerebral arteries, was set at 100% and used to determine the relative density of specific populations of autonomic and sensory nerve fibres. In all four cerebral arteries, the majority of nerve fibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase (TH) immunoreactivity, occupying 6.2-13.3% and 5.8-7.5% of the total vessel wall area, respectively. Vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin-gene-related peptide (CGRP) were detected at lower densities. The pharmacological study performed on small circular segments with an intact endothelium revealed that, in all four cerebral arteries, NPY was a more potent constrictor than noradrenaline (NA). The rank order of potency for relaxant agents was CGRP = SP > VIP > ACh in the PCA and MCA, and SP = CGRP > VIP > ACh in the BA and ACA. The correlation between immunostained nerve area and the agonist potency suggested that the denser the peptidergic nerve-supply, the lower the sensitivity to the agonist.
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PMID:Peptidergic innervation of guinea-pig brain vessels: comparison with immunohistochemistry and in vitro pharmacology in rostrally and caudally located arteries. 880 Dec 68


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