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)

The "touchdown" polymerase chain reaction (PCR) technique has been applied to analyze expression of the neuron-specific protein, PGP9.5, and tyrosine hydroxylase (TH) genes for detection of minimal residual neuroblastoma cells in bone marrow and peripheral blood. PGP9.5 and TH gene products were not detected in any normal samples (n = 72) examined. However, in patients more than 1 year of age with stage III and IV neuroblastoma PGP9.5 mRNA was detected in six of seven bone marrow samples and in four of eight peripheral blood samples, and TH mRNA in four of seven and three of eight, respectively. The detection sensitivity was up to 10(-6) to 10(-7) micrograms of total cellular RNA for PGP9.5 and 10(-4) micrograms for TH. Among forty bone marrow specimens from nineteen patients with neuroblastoma both PGP9.5 and TH mRNAs were detected in six, and only PGP9.5 mRNA was detected in ten. Since detection of PGP9.5 and TH gene transcripts by the "touchdown" PCR was highly specific and sensitive, it might be most informative at present to carry out both PGP9.5 and TH mRNA assays for minimal residual neuroblastoma cells in blood and bone marrow.
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PMID:Detection of the PGP9.5 and tyrosine hydroxylase mRNAs for minimal residual neuroblastoma cells in bone marrow and peripheral blood. 959 38

Regeneration of sensory and adrenergic nerves in the skin was studied in rats. The aim was to investigate the effect of reanastomosing the cut nerve ends of the nerve trunk leading to the microvascular groin flap. Reinnervation was demonstrated immunohistochemically using calcitonin gene-related peptide (CGRP) as marker for sensory nerves, neuropeptide Y (NPY) and tyrosine hydroxylase (TH) as markers for adrenergic nerves and Protein Gene Product 9.5 (PGP 9.5) as general neuronal marker. It was demonstrated that reanastomosing of the nerve trunk was favourable for both the sensory and sympathetic reinnervation of microsurgical flaps.
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PMID:Reinnervation after nerve suture in rat groin flaps. 963 85

Atrioventricular (AV) nodal conduction time is known to be modulated by the autonomic nervous system. The presence of numerous parasympathetic and sympathetic nerve fibres in association with conduction tissue in the heart is well authenticated. In this study, confocal microscopy was used to image the distribution of antibodies directed against the general neuronal marker PGP 9.5, tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and beta1 and beta2-adrenoreceptors. Serial 12 microm sections of fresh frozen tissue taken from the frontal plane of the rat atrioventricular node, His bundle and bundle branches were processed for histology, acetylcholinesterase (AChE) activity and immunohistochemistry. It was found that the AV and ventricular conduction systems were more densely innervated than the atrial and ventricular myocardium as revealed by PGP 9.5 immunoreactivity. Furthermore, the transitional cell region was more densely innervated than the midnodal cell region, while spatial distribution of total innervation was uniform throughout all AV nodal regions. AChE-reactive nerve processes were found throughout the AV and ventricular conduction systems, the spatial distribution of which was nonuniform exhibiting a paucity of AChE-reactive nerve processes in the central midnodal cell region and a preponderance in the circumferential transitional cell region. TH-immunoreactivity was uniformly distributed throughout the AV and ventricular conduction systems including the central midnodal and circumferential transitional cell regions. Beta1-adrenoreceptors were found throughout the AV and ventricular conduction systems with a preponderance in the circumferential transitional cell region. Beta2-adrenoreceptors were localised predominantly in AV and ventricular conduction systems with a paucity of expression in the circumferential transitional cell region. These results demonstrate that the overall uniform distribution of total nerve processes is comprised of nonuniformly distributed subpopulations of parasympathetic and sympathetic nerve processes. The observation that the midnodal cell region exhibits a differential spatial pattern of parasympathetic and sympathetic innervation suggests multiple sites for modulation of impulse conduction within this region. Moreover, the localisation of beta2-ARs in the AV conduction system, with an absence of expression in the circumferential transitional cell layer, suggests that subtype-specific pharmacological agents may have distinct effects upon AV nodal conduction.
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PMID:Spatial distribution of nerve processes and beta-adrenoreceptors in the rat atrioventricular node. 972 79

The accessory olfactory bulb (AOB) is a primary center of the vomeronasal system. In the dog, the position and morphology of the AOB remained vague for a long time. Recently, the morphological characteristics of the dog AOB were demonstrated by means of lectin-histochemical, histological, and immunohistochemical staining, although the distribution of each kind of neuron, especially granule cells, remains controversial in the dog AOB. In the present study, we examined the distribution of neuronal elements in the dog AOB by means of immunohistochemical and enzyme-histochemical staining. Horizontal paraffin or frozen sections of the dog AOB were immunostained with antisera against protein gene product 9.5 (PGP 9.5), brain nitric oxide synthase (NOS), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), substance P (SP), and vasoactive intestinal polypeptide (VIP) by avidin-biotin peroxidase complex method. In addition, frozen sections were stained enzyme-histochemically for NADPH-diaphorase. In the dog AOB, vomeronasal nerve fibers, glomeruli, and mitral/tufted cells were PGP 9.5-immunopositive. Mitral/tufted cells were observed in the glomerular layer (GL) and the neuronal cell layer (NCL). In the NCL, a small number of NOS-, GAD-, and SP-immunopositive and NADPH-diaphorase positive granule cells were observed. In the GL, GAD-, TH-, and VIP-immunopositive periglomerular cells were observed. In the GL and the NCL, TH-, and VIP-immunopositive short axon cells were also observed. In addition to these neurons, TH- and SP-immunopositive afferent fibers were observed in the GL and the NCL. We could distinctly demonstrate the distribution of neuronal elements in the dog AOB. Since only a small number of granule cells were present in the dog AOB, the dog AOB did not display such a well-developed GCL as observed in the other mammals.
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PMID:Immunohistochemical and enzyme-histochemical study on the accessory olfactory bulb of the dog. 981 Dec 17

Mammalian intrinsic cardiac neurons subserve different functions in different cardiac regions, but the regional anatomical organisation of the intracardiac nervous system is not well understood. We investigated the quantitative and qualitative distribution of cholinergic and adrenergic elements, and the intracardiac pathways of extrinsic cardiac nerves, in whole-mount preparations of guinea pig atria. Protein gene product 9.5 immunoreactivity (PGP 9.5-IR) marked intracardiac neuronal elements; immunoreactions for choline acetyltransferase (ChAT-IR) and tyrosine hydroxylase (TH-IR) distinguished cholinergic and adrenergic components, respectively. Catecholamine-containing components were identified by aldehyde-induced fluorescence histochemistry. Mean total number of atrial neurons was 1510+/-251 (SE); 85% of these occurred in ganglia of < or = 20 neurons. All neuronal somata expressing PGP 9.5-IR also expressed ChAT-IR, suggesting that these neurons were cholinergic. Right (RA) and left (LA) atria had statistically similar neuronal densities (6.4+/-1.2 and 2.4+/-0.7 neurons/mm2, respectively; analysis of variance, P< or =0.05). Neurons in RA were concentrated intercavally; LA neurons were concentrated near pulmonary vein ostia. Greatest density occurred in the interatrial septum (16.3+/-4.0 neurons/mm2). No neuronal somata expressed TH-IR or contained detectable amines but these elements were expressed by somata of small cells (mean total 124+/-33) throughout the atria, primarily associated with ganglia. Amine- and TH- containing varicosities were also present in ganglia, representing potential sites for adrenergic modulation of ganglionic neurotransmission. Branches of extrinsic cardiopulmonary and vagus nerves were distributed to all parts of both atria. The organisation of the intracardiac nervous system revealed in this study will facilitate further investigations of regional autonomic control of the heart.
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PMID:Regional distribution and extrinsic innervation of intrinsic cardiac neurons in the guinea pig. 1032 Feb 13

Functional data indicate that neurons in distinct regions of the heart exert preferential regional cardiac control. To date the regional distribution of specific types of neurons within the intrinsic cardiac nervous system remains unknown, as does their associations with distinct neurotransmitter and/or neuromodulatory profiles. This study was designed to ascertain: (1) the distribution of different classes of neurons within the intrinsic cardiac nervous system as determined by microscopic analysis; (2) the neurochemical profiles of neurons in differing atrial loci; (3) which neurochemicals are co-localized within specific populations of intrinsic cardiac neurons; and (4) the distribution of specific sub-populations of neurons expressing specific immunoreactivities. Taking advantage of confocal laser scanning microscopy and distinct immunoreactive fluorescent markers in various double-label combinations, several sub-populations of intrinsic cardiac neurons were identified. Of all identified neurons, 85-90% were located in ganglia (ganglionic neurons), the rest being isolated (individual neurons). The two general neuronal markers protein gene product 9.5 (PGP 9.5) and microtubule-associated protein (MAP-2) were associated with neurons clustered primarily in the interatrial septum and around the origins of the two vena cavae. Ganglia (group 1) contained three sub-populations of neurons: approx. 80% of ganglionic neurons were large (15-40 microm diameters; group 1a) and approx. 20% had smaller diameters (less than 15 microm; group 1b). All of these neurons were PGP-immunoreactive, exhibiting choline acetyltransferase (ChAT) immunoreactivity (IR), tyrosine hydroxylase (TH) IR, neuropeptide Y (NPY) IR, vasoactive peptide (VIP) IR and substance P (SP) IR. The remaining 5% of ganglionic neurons were small (group 1c; less than 20 microm). These displayed TH immunoreactivity but not MAP, PGP, CHAT, NPY or SP immunoreactivity. Ten to fifteen percent of all neurons loosely distributed outside of ganglia were small (10-25 microm) and located primarily around the origin of the superior vena cava. They displayed immunoreactivity to TH, ChAT, VIP, NPY and SP, but not to MAP-2 or PGP 9.5. These data provide anatomical and immunohistochemical evidence for specific localization of differing populations of intrinsic cardiac neurons with respect to their size, ganglionic distributions and capacity to express multiple neurotransmitters. Although the functional importance of such a regional distribution of differing populations of intrinsic cardiac neurons remains unknown, these anatomical data support the thesis that unique clustering of specific populations of neurons within this nervous system represents the anatomical substrate for complex local cardiac regulatory phenomena occurring at the level of the target organ.
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PMID:Distribution of intrinsic cardiac neurons in whole-mount guinea pig atria identified by multiple neurochemical coding. A confocal microscope study. 1046 Apr 88

By using immunohistochemistry and antibodies to a general nerve marker, protein gene product (PGP) 9.5, the overall innervation at the extensor carpi radialis brevis (ECRB) muscle origin was investigated in patients with tennis elbow and in healthy controls. The autonomic innervation was studied by using antibodies to neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). The sensory innervation was visualized by using antibodies to substance P and calcitonin gene-related peptide. PGP 9.5 immunoreactions were detected in association with small blood vessels and arteries and within nerve bundles. There was, however, heterogeneity in the perivascular nerve fiber distribution since some blood vessels exhibited a high degree of PGP 9.5 innervation and some negligible or no such innervation at all. There was marked TH/NPY innervation in the walls of a subpopulation of the arteries, basically no VIP-containing nerves, and sensory innervation restricted to the small blood vessels. These observations show that the ECRB muscle origin is supplied with heterogeneously distributed sympathetic and sensory innervations and, furthermore, that there appears to be an imbalance between the vasoconstrictor and vasodilator innervations along the vascular tree in this region.
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PMID:Sympathetic and sensory innervations are heterogeneously distributed in relation to the blood vessels at the extensor carpi radialis brevis muscle origin of man. 1046 Sep 73

We analyzed the presence of autonomic nerve fibers in the interface membranes (n = 9) surrounding aseptic loosened hip prostheses by immunohistochemistry. The study focused on the autonomic messengers neuropeptide Y (NPY), tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of noradrenaline (NA), and vasoactive intestinal polypeptide (VIP). Protein gene product (PGP) 9.5, a general marker of peripheral nerve fibers, was also analyzed to establish the neuronal character of the immunoreactive structures. PGP 9.5-positive and NPY-positive nerve fibers were identified in all 9 samples, and VIP-immunoreactive and TH-immunoreactive fibers were found in 7. There was a difference in the distribution of nerve fibers both between and within the samples. Among the neuropeptides analyzed, NPY was most abundant. NPY-positive and TH-positive fibers were predominantly found around the blood vessel walls forming varicose nerve terminals. VIP-positive fibers were mainly observed as thin varicose nerve terminals with no relationship to blood vessels. Autonomic neuropeptides exert not only vasoactive and immunoregulatory effects, but also have been found to have direct effects on bone tissue. Moreover, the autonomic nervous system has been strongly implicated in nociception and inflammation. Neuronal NPY, TH, and VIP in the interface membrane may prove to contribute to the pathologic mechanisms leading to aseptic loosening of hip prostheses.
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PMID:Autonomic neuropeptides in the interface membrane of aseptic loose hip prostheses. 1047 60

Previous studies have shown that chronic administration of oestrogen to prepubertal rats reduces the total content of noradrenaline in the uterine horn, abolishes myometrial noradrenergic innervation and reduces noradrenaline-fluorescence intensity of intrauterine perivascular nerve fibres. The mechanisms underlying these changes are not known. In the present study we have analysed the effects of prepubertal chronic oestrogen treatment on the synthesis of noradrenaline in the rat uterine sympathetic nerves using biochemical and immunohistochemical approaches. Tyrosine hydroxylase activity was evaluated biochemically, by measuring the in vivo accumulation of dihydroxyphenylalanine (DOPA) in the presence of a DOPA-decarboxylase inhibitor. In addition, nerve fibres were visualised immunohistochemically using antibodies against tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DbetaH) and the general marker protein gene product 9.5 (PGP 9.5). After chronic oestrogen treatment, the total content of noradrenaline of the uterine horn was reduced, whereas the total content of DOPA was increased. In controls, TH-immunoreactive, DbetaH-immunoreactive and PGP 9.5-immunoreactive nerve fibres were distributed in both the circular and longitudinal myometrial layers and in the blood vessels of the intran-myometrial region. After chronic oestrogen treatment the only fibres recognised by the three antibodies were those associated with the blood vessels, but no myometrial-associated fibres could be recognised. These results suggest that noradrenaline synthesis is selectively reduced in myometrial-associated uterine sympathetic nerves, but is preserved in perivascular sympathetic nerves. The increased DOPA levels measured after chronic exposure to oestrogen was interpreted as the consequence of the substantial increase in size and number of blood vessels observed in the uterus of oestrogen-treated animals. A possible neurodegenerative effect of oestrogen on myometrial sympathetic fibres is discussed.
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PMID:Differential effects of prepubertal chronic oestrogen treatment on the synthesis of noradrenaline in uterine myometrial and perivascular sympathetic nerves. 1047 65

Neurotransmitters are known to play an important role in the development of the nervous system. We recently generated transgenic mice that ectopically express tyrosine hydroxylase (TH) and thereby produce dopamine (DA) de novo in pinealocytes of the pineal gland (PG). The transgenic PG also exhibited a dramatic decrease in TH-immunoreactive (IR) fibers putatively arising from the superior cervical ganglion (SCG) (Cho et al. [1996] Proc Natl Acad Sci USA 93:2862-2866). In the current study, however, we found that there was no reduction in the number of fibers immunostained for neurofilament protein or PGP9.5, markers known to be heavily localized in fibers, despite the reduction of TH fiber density. Therefore, we investigated whether the decreased TH-IR fiber density is the consequence of reduced sympathetic innervation, or a decrease in TH expression within innervating fibers. Immunohistochemical analysis comparing control and transgenic PG demonstrated no apparent differences in numbers of NPY- and aromatic-L-amino acid decarboxylase (AADC)-IR fibers, indicating that TH expression is decreased in a normal number of innervating fibers. Furthermore, presynaptic neurons in the transgenic SCG showed abnormal and heterogeneous TH immunoreactivity and reduced TH and norepinephrine transporter (NET) mRNA levels. These results show that ectopic DA production in the PG lowers TH and NET gene expression in the SCG without altering sympathetic innervation to the PG and suggest that the alteration of target neurotransmitter phenotype may influence gene expression of phenotype-specific proteins in projecting neurons.
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PMID:Altered presynaptic gene expression in transgenic mice producing dopamine in the pineal gland. 1050 12


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