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

Two cases of duodenal gangliocytic paraganglioma were studied by means of immunocytochemical methods using 41 kinds of antibodies. The tumors consisted of three histological types; carcinoid, ganglioneuroma and paraganglioma. Tumors of both cases exhibited immunoreactivity to at least one or as many as three of the following: calcitonin, calcitonin-gene related peptide, endocrine granule constituent, Leu7, neuropeptide Y and basic fibroblast growth factor. In addition, these tumors were also immunopositive for neuron specific enolase, S-100 protein, neurofilament protein, pancreatic polypeptide, chromogranin A, somatostatin, leuenkephalin, substance P and vasoactive intestinal peptide, as has been described in previous reports. In one case, tumor cells were immunopositive for adrenocorticotropin, bombesin, gastrin releasing peptide, myelin basic protein, neuroendocrine marker and tyrosine hydroxylase. Moreover, paraganglioma cells of tumors showed both argyrophilia and argentaffinity. These results suggest that duodenal gangliocytic paraganglioma may originate from embryonic neuroinsular complex.
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PMID:Two cases of duodenal gangliocytic paraganglioma: immunocytochemical characteristics. 882 94

Pheochromocytomas in mice are rare tumors, and their expression of functional markers has not previously been assessed. In this study, 29 spontaneously occurring mouse pheochromocytomas were characterized morphologically and immunohistochemically to determine whether there are functional correlates to previously described morphological features and to provide a database for comparison with tumors that arise in genetically engineered animals. The tumors were derived from 28 mice 828-1,489 days old, of three genotypes. Considerable cytological and architectural polymorphism was observed both within and between tumors. Most of the tumor cells were comparable in size to normal chromaffin cells or were larger. Small basophilic cells, which are the predominant cell type in rat pheochromocytomas, were usually in the minority. All of the tumors and most of the cells within individual tumors expressed immunoreactive tyrosine hydroxylase (TH). The tumors were variably positive for phenylethanolamine-N-methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a global association of specific cytological features with expression of TH, PNMT, or CGA, although cells of similar appearance often shared similar immunoreactivities within individual tumors. Small basophilic cells could be either PNMT-positive or PNMT-negative. The frequency, morphology, and immunophenotype of mouse pheochromocytomas suggest that the mouse may be more appropriate than the rat as a model for human adrenal medullary pathology. In addition, the expression of immunoreactive PNMT by mouse pheochromocytomas suggests that these tumors are a potential source of epinephrine-producing cell lines, for which adequate models currently do not exist.
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PMID:Immunohistochemical and morphological characterization of spontaneously occurring pheochromocytomas in the aging mouse. 888 77

The expression of the neural cell adhesion molecule, chromogranin A, and catecholamine-synthesizing enzymes (tyrosine hydroxylase and phenylethanolamine N-methyl transferase) in adrenal medulla and para-aortic bodies (paraganglia) of the adult rabbit, was studied by immunofluorescence. The specificity of the neural cell adhesion molecule antibody employed was demonstrated on rabbit tissue by immunoblotting. Neural cell adhesion molecule was found to be expressed not only by adrenal medullary cells but also by extra-adrenal chromaffin cells present in para-aortic bodies. These paraganglionic cells were as intensely immunolabelled for chromogranin A as adrenal medullary chromaffin cells. They were also labelled for the catecholamine-synthesizing enzymes tested here. However, their levels of the adrenalin-synthesizing enzyme phenylethanolamine N-methyl transferase were lower than those of medullary chromaffin cells.
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PMID:Immunocytochemical localization of NCAM and catecholamine-synthesizing enzymes in rabbit intra- and extra-adrenal chromaffin tissue. 895 May 95

The parathyroid glands of the adult rat harbor a number of neuroendocrine markers, biologically active peptides and "classical" neuromessengers in addition to parathyroid hormone (PTH). Their appearance during parathyroid development is, however, not known. In the present study we have examined several neuroendocrine markers and neuromessengers in the parathyroid glands of the developing rat [embryonic stage 21(E21), newborn, 1, 2, 3, 4 week old, and adult rats] using immunocytochemistry. Chromogranin A- and PTH-mRNA were also examined by in situ hybridization and the mRNA levels were quantitated by computerized image analysis. Protein gene product 9.5- and synaptophysin-containing nerve fibers appeared already before birth and then gradually increased in number postnatally, and at the age of 4 weeks the nerve fibers were moderate in number to numerous. Nerve fibers containing calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide also increased gradually in number, while galanin-, substance P- and tyrosine hydroxylase-containing fibers remained few throughout development. The glandular cells expressed chromogranin A, pancreastatin and PTH already before birth. The levels of chromogranin A- and PTH-mRNA were low at E21 and increased markedly at birth; chromogranin A mRNA levels had increased even more at 1 week postnatally. Three to 4 weeks after birth the levels of PTH- and chromogranin A mRNA again increased, then stabilized at a slightly lower level in the adult rat. Our findings demonstrate that the parathyroid glands of rat are already innervated and express PTH and chromogranin A before birth and that the density of peptide-containing nerve fibers changes during development. The stepwise increases of PTH- and chromogranin A mRNAs during development indicate marked changes in parathyroid activity occurring at birth and at weaning.
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PMID:Developmental expression of neuronal and endocrine markers in the parathyroid glands of the rat. 919 26

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.
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PMID:Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. 922 69

We have shown previously that platelet-derived growth factor (PDGF) has trophic effects on dopaminergic neurons in vitro. We now examined a mouse neuroblastoma cell line, NB41, for its response to PDGF and studied their phenotypic characteristics following introduction of an antisense PDGF beta-receptor RNA. NB41 cells produce both PDGF-AA and -BB; however, they carry only PDGF beta-receptors, responding to BB but not to AA. Culturing the cells with PDGF-BB induced mRNA for c-fos and PDGF-beta receptor as well as that of neuron-specific enzyme, tyrosine hydroxylase. In contrast, mRNA of chromogranin A, which is produced by chromaffin cells, decreased. Introduction of an antisense PDGF beta-receptor RNA in NB41 cells completely suppressed neurite extension and cell growth. We compared the PDGF-beta receptor sense and antisense clones for their survival. Following serum withdrawal, NB41 cells showed a DNA ladder, which by an addition of the neurotoxin, 6-hydroxy dopamine (6-OHDA), resulted in a further enhancement of the DNA ladder. The addition of PDGF-BB prior to 6-OHDA rescued cells from undergoing apoptosis, seen as a reduction of the DNA ladder. The antisense clone, regardless of the presence of PDGF-BB in the culture, showed a pronounced DNA ladder after serum withdrawal, which was further enhanced by the addition of 6-OHDA.
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PMID:Characterization of platelet-derived growth factor (PDGF) action on a mouse neuroblastoma cell line, NB41, by introduction of an antisense PDGF beta-receptor RNA. 926 95

Recently we have identified a dopamine-producing system in the gastric mucosa of rats. All the available morphological data suggest that parietal cells synthesize dopamine. In the present study we investigated the dopaminergic characteristics of isolated parietal cells by different methods. Mixed gastric mucosal cells were isolated and size-fractionated by elutriation. The proportion of neurons, parietal and endocrine cells in the fractions were determined by immunocytochemistry (ICC) using antibodies to neurofilament, proton pump and chromogranin A, respectively. No neurons were found in any of the cell preparations, while 56% parietal cell and 0.0% endocrine cell were achieved in the parietally enriched fraction. By Western blot, a tyrosine hydroxylase (TH, the rate-limiting enzyme of the catecholamine synthesis) immunoreactive protein species was demonstrated in isolated mucosal cells, comigrating with the TH immunoreactivity from PC12 cells. The TH immunoreactivity was colocalized to parietal cells by ICC. Dopamine transporter (DAT), a regulator of extracellular/intracellular dopamine balance in the nervous system, was also demonstrated in parietal cells. A significant amount of dopamine and DOPA were measured by HPLC (13.4 and 9.57 pg/10(6) cell, respectively) in parietally enriched cell fraction. Since this enriched cell fraction was virtually clear of both neurons and endocrine cells, demonstration of TH enzyme, DAT and dopamine in this fraction confirms that the parietal cell population might be a major source of dopamine in the rat stomach, supporting our previous results achieved using whole tissue samples.
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PMID:Dopaminergic characteristics of isolated parietal cells from rats. 940 3

The family of chromogranins/secretogranin peptides comprises three major subtypes: chromogranin A, chromogranin B and secretogranin II. We have characterized these proteins in rat vas deferens and pelvic ganglia by using two approaches. Firstly, extracts of rat vas deferens were subjected to molecular sieve chromatography followed by radioimmunoassay. The results indicate that, in the peripheral nerves of this organ, chromogranin B and secretogranin II are processed to small peptides, i.e. PE-11 and secretoneuron, respectively. Secondly, we investigated the localization of each of these peptides in the rat pelvic ganglia and vas deferens. Comparisons with the distribution of tyrosine hydroxylase, choline acetyltransferase, vesicular acetylcholine transporter and SV2 were carried out in double labelling studies. All tyrosine hydroxylase-positive neurons contained neuropeptide Y, but many neuropeptide Y-containing neurons were negative for tyrosine hydroxylase. In the pelvic ganglia, chromogranin A was widely localized in the neuropeptide-positive neurons and 65% of chromogranin A-containing neurons were positive for tyrosine hydroxylase, suggesting their adrenergic nature. However, in nerve terminals of the vas deferens, chromogranin A was present at very low, or undetectable, levels. The chromogranin B-derived peptide PE-11, on the other hand, was absent from the large-sized, tyrosine hydroxylase-positive neurons, but present in some small-sized neurons that were choline acetyltransferase/vesicular acetylcholine transporter-positive and tyrosine hydroxylase-negative. In the vas deferens, PE-11 was present with intense immunoreactivity in nerve terminals of the lamina propria beneath the epithelium, but it was very sparse in the muscular layer and co-localized with vesicular acetylcholine transporter-like immunoreactivity, suggesting a cholinergic nature. The secretogranin II-derived peptide secretoneurin was distributed with strong immunoreactivity in the somata of pelvic ganglion neurons, 72% of which also contained tyrosine hydroxylase, as well as in nerve terminals in the muscular layer and the lamina propria of the vas deferens. Most, if not all, secretoneurin-positive terminals in the pelvic ganglia and the vas deferens were positive for choline acetyltransferase/vesicular acetylcholine transporter-like immunoreactivity. Retrograde tracing with FluoroGold demonstrated that the majority of FluoroGold-labelled neurons in the pelvic ganglia were positive for either chromogranin A or secretoneurin. The present study indicates that chromogranins A and B and secretogranin II are proteolytically processed to a high degree in the nerves of the rat vas deferens. Furthermore, they are heterogeneously localized in subsets of neurons of the pelvic ganglia and in different sets of nerve terminals in the vas deferens, suggesting that each of these peptides may play distinct roles in neurons of the autonomic nervous system to the vas deferens.
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PMID:Distribution of chromogranins A and B and secretogranin II (secretoneurin) in rat pelvic neurons and vas deferens. 952 81

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.
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PMID:Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. 959 31

In the chicken, glomus cells are widely distributed not only in the carotid body but also in the wall of the common carotid artery and around each artery arising from the common carotid artery. Effects of chronic isocapnic hypoxia on the chicken carotid body and the glomus cells in and around the arteries were examined by immunohistochemistry and electron microscopy. In chickens exposed to isocapnic hypoxia for 35 days, three- to four-fold increase of the carotid body volume was induced. Immunoreactivity for tyrosine hydroxylase of glomus cells almost completely disappeared. Dense networks of TuJ1-immunoreactive nerve fibers were unchanged, whereas peptidergic nerve fibers, i.e., substance P-, calcitonin gene-related peptide-, vasoactive intestinal peptide-, galanin- and neuropeptide Y-immunoreactive fibers, were decreased in and around the carotid body. At the electron microscopic level, increased secretory activity of the glomus cells was verified. Mature dense-cored vesicles were markedly decreased, although prosecretory granules were numerous around Golgi complexes. Many immature glomus cells filled with rough endoplasmic reticulum and free ribosomes, also appeared in the carotid bodies of hypoxic chickens. In contrast to the carotid body, the glomus cells located in the wall of the common carotid artery revealed no changes after long-term hypoxia. The cells in the hypoxic chickens, as well as normal controls, expressed intense immunoreactivity for neuropeptide Y, serotonin and chromogranin A. Furthermore, a large number of dense-cored vesicles were distributed throughout the cytoplasm. The glomus cells around each artery arising from the common carotid artery were affected by hypoxia, although the degree of their response to hypoxia varied depending on the locations.
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PMID:Different effects of prolonged isocapnic hypoxia on the carotid body and the glomus cells in the wall of the common carotid artery of the chicken. 973 64


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