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)

The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.
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PMID:Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. 1019 70

Among the dopaminergic neurons in substantia nigra pars compacta and in the ventral tegmental area, subpopulations express the calcium-binding proteins calbindin (CB) and calretinin (CR), and the CB-containing neurons are supposed to be less prone to degeneration in Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons. Using free-floating roller-tube (FFRT) cultures derived from fetal rat (E14) ventral mesencephalon we found that GDNF (10 ng/ml) significantly increased the number of surviving tyrosine hydroxylase (TH)-immunoreactive neurons. The possible effects of GDNF treatment on CB-immunoreactive (CB-ir) and CR-ir neurons in such cultures were examined in the present study. The neuronal cell densities were measured by quantifying the numbers of CB-ir and CR-ir neurons in areas of sections through the most extensive parts of the spherical cultures. In 4-day-old and 8-day-old cultures GDNF treatment increased the density of CB-ir neurons by 50% and 59%, respectively. Partial co-existence of TH and CB was shown using the method of double immunolabeling. The density of CR-containing neurons was unaffected by GDNF treatment as confirmed by Western blotting for CR. Parallel effects of GDNF treatment were obtained for cultures of human fetal ventral mesencephalon (8 weeks postconception). In conclusion, our findings identify GDNF as a potent factor for fetal rat and human nigral CB-ir neurons able to promote their survival in culture. Referring to a suggested neuroprotective role of CB, the results may be of relevance in the context of neuronal transplantation of patients suffering from severe Parkinson's disease.
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PMID:GDNF increases the density of cells containing calbindin but not of cells containing calretinin in cultured rat and human fetal nigral tissue. 1033 73

The electrophysiological and neurochemical characteristics of the nondopaminergic nigrostriatal (NO-DA) cells and their functional response to the degeneration of dopaminergic nigrostriatal (DA) cells were studied. Three different criteria were used to identify NO-DA cells: (1) antidromic response to striatal stimulation with an electrophysiological behavior (firing rate, interspike interval variability, and conduction velocity) different from that of DA cells; (2) retrograde labeling after striatal injection of HRP but showing immunonegativity for DA cell markers (tyrosine hydroxylase, calretinin, calbindin-D28k, and cholecystokinin); and (3) resistance to neurotoxic effect of 6-hydroxydomine (6-OHDA). Our results showed that under normal conditions, 5-8% of nigrostriatal neurons are immunoreactive for GABA, glutamic acid decarboxylase, and parvalbumin, markers of GABAergic neurons, a percentage that reached 81-84% after 6-OHDA injection. Electrophysiologically, NO-DA cells showed a behavior similar to that found in other nigral GABAergic (nigrothalamic) cells. In addition, the 6-OHDA degeneration of DA cells induced a modification of their electrophysiological pattern similar to that found in GABAergic nigrothalamic neurons. Taken together, the present data indicate the existence of a small GABAergic nigrostriatal pathway and suggest their involvement in the pathophysiology of Parkinson's disease.
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PMID:Electrophysiological and morphological evidence for a GABAergic nigrostriatal pathway. 1034 Dec 66

Parkinson's disease (PD) is characterized by progressive neuronal loss associated with Lewy bodies in many subcortical nuclei leading to multiple biochemical and pathophysiological changes of clinical relevance. Loss of nigral neurons causing striatal dopamine deficiency is related to both the duration and clinical stages (severity) of the disease. The clinical subtypes of PD have different morphological lesion patterns: a) The akinetic-rigid type shows more severe cell loss in the ventrolateral part of substantia nigra zona compacta (SNZC) that projects to the dorsal putamen than the medial part projecting to caudate nucleus and anterior putamen, with negative correlation between SNZC cell counts, severity of akinesia-rigidity, and dopamine loss in the posterior putamen. Reduced dopaminergic input causes overactivity of the GABA ergic inhibitory striatal neurons projecting via the "indirect loop" to SN zona reticulata (SNZR) and medial pallidum (GPI) leading to inhibition of the glutamatergic thalamo-cortical motor loop and reduced cortical activation. b) The tremor-dominant type shows more severe neuron loss in medial than in lateral SNZC and damage to the retrorubral field A8 containing only few tyrosine hydroxylase and dopamine transporter immunoreactive (IR) neurons but mainly calretinin-IR cells. A8 that is rather preserved in rigid-akinetic PD (protective role of calcium-binding protein?) projects to the matrix of dorsolateral striatum and ventromedial thalamus. Together with area A10 it influences the strial efflux via SNZR to thalamus and from there to prefrontal cortex. Rest tremor in PD is associated with increased metabolism in the thalamus, subthalamus, pons, and premotor-cortical network suggesting an increased functional activity of thalamo-motor projections. In essential tremor, no significant pathomorphological changes but overactivity of cerebello-thalamic loop have been observed. c) In the akinetic-rigid forms of multisystem atrophy, degeneration is more severe in the lateral SNZC with severe loss of calbindin-IR cells reflecting initial degeneration of the striatal matrix in the caudal putamen with transsynaptic degeneration of striatonigral efferences that remain intact in PD. This fact and loss of striatal D2 receptors--as in advanced stages of PD--are reasons for negative response to L-dopa substitution. These data suggest different pathophysiological mechanisms of the clinical subtypes of PD that have important therapeutic implications. d) Involvement of extranigral structures in PD includes the mesocortical dopaminergic system, the noradrenergic locus coeruleus, dorsal vagal nucleus and medullary nuclei, serotonergic dorsal raphe, nucleus basalis of Meynert and other cholinergic brainstem nuclei, e.g. Westphal-Edinger nucleus (controlling pupillomotor function), posterolateral hypothalamus and the limbic system, e.g. amygdaloid nucleus, part of hippocampal formation, limbic thalamic nuclei with prefrontal projections, etc. Damage to multiple neuronal systems by the progressing degenerative process causing complex biochemical changes may explain the variable clinical picture of PD including vegetative, behavioural and cognitive dysfunctions, depression, pharmacotoxic psychoses, etc. Future comparative clinico-morphological and pathobiochemical studies will further elucidate the pathophysiological basis of specific clinical symptoms of PD and related disorders providing a broader basis for effective treatment strategies. Parkinson's disease (PD) is characterized by progressive degeneration of the nigrostriatal dopaminergic system and other subcortical neuronal systems leading to striatal dopamine deficiency and other biochemical deficits related to the variable clinical signs and symptoms of the disorder. (ABSTRACT TRUNCATED)
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PMID:Post mortem studies in Parkinson's disease--is it possible to detect brain areas for specific symptoms? 1037 Sep 1

The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture.
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PMID:Chemical heterogeneity of the striosomal compartment in the human striatum. 1049 46

We used triple-labeling immunohistochemistry in rat midbrain sections to identify dopaminergic neurons that contain either one or both of the calcium-binding proteins, calretinin (CR) and calbindin-D28k (CB). Midbrain dopaminergic neurons were immunohistochemically labeled for tyrosine hydroxylase (TH), CR, and CB. In the substantia nigra pars compacta (SNC), TH+/CR+/CB+ cells were clustered in two regions: the dorsal tier of the rostral SNC and the medial part of the intermediate SNC. The ventral tier of the rostral SNC mainly comprised both TH+/CR+/CB- and TH+/CR-/CB- cells. The lateral part of the intermediate SNC and the caudal SNC primarily consisted of TH+/CR-/CB- cells. Throughout the extent of the SNC, approximately half of the TH+ neurons were stained for neither CR nor CB, while the remaining TH+ populations were labeled for CR and/or CB. Throughout the ventral tegmental area, TH+/CR+/CB+ cells, TH+/CR+/CB- cells, TH+/CR-/CB+ cells, and TH+/CR-/CB- cells were found generally scattered, though the TH+/CR-/CB- cells were dominant in number. In the substantia nigra pars lateralis, interfascicular nucleus, and caudal linear nucleus, more than half of the TH+ cells were stained for both CR and CB. In the retrorubral field, two-thirds of the TH+ neurons contained neither protein. The present findings suggest that the SNC can be divided into subcompartments based on the distribution of dopaminergic neurons that contain calcium-binding proteins. Furthermore, because CR and CB likely contribute to calcium homeostasis by buffering intracellular calcium concentrations, midbrain dopaminergic neurons containing one or both of these calcium-binding proteins may have a higher calcium-buffering capacity than those lacking the two proteins.
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PMID:Calretinin and calbindin-D28k in dopaminergic neurons of the rat midbrain: a triple-labeling immunohistochemical study. 1053 20

Caldendrin is a novel calcium-binding protein confined to the somatodendritic compartment of neurons. Here we have studied the expression pattern of caldendrin in the rat retina. First we assessed the distribution of caldendrin transcripts in the adult and developing retina by in situ hybridization. In the adult retina, transcripts are expressed mainly in the inner half of the inner nuclear layer (INL) and to a lesser extent in the ganglion cell layer (GCL). During development labeling of the inner part of the cytoblast layer, where amacrine cells reside, is already present at postnatal day 1 (P1). The intensity of hybridization signal in this sublamina of the developing INL increases up to P8, whereas significant labeling in the GCL was first found at P14, coinciding with eye opening. Immunodetection with a polyclonal antibody revealed intensive staining of cells in the inner retina, which are presumably mainly amacrine and significantly fewer bipolar and ganglion cells. All parvalbumin-containing All amacrines were immunopositive for caldendrin. Colocalization with calbindin was found in cone bipolar cells, the majority of AII amacrines, and calbindin-positive cells in the GCL. In the GCL, caldendrin was also colocalized with calretinin-immunopositive cells. Most caldendrin-positive amacrine cells in the adult rat retina were glycinergic and only a few were GABAergic. In retinal flat mounts, it was confirmed that less than 10% of retrogradely labeled retinal ganglion cells (RGC) are caldendrin-positive. Caldendrin immunoreactivity does not colocalize with tyrosine hydroxylase, VIP, substance P and somatostatin immunoreactivity. In summary, caldendrin expression is regulated differentially in retinal cell types during development and is restricted to a subpopulation of amacrine, bipolar, and ganglion cells, suggesting specific functions in the developing and mature retina.
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PMID:The cytoskeleton-associated neuronal calcium-binding protein caldendrin is expressed in a subset of amacrine, bipolar and ganglion cells of the rat retina. 1055 36

A certain calcium binding protein (CaBP) has been known to exert a neuroprotective effect in various neurodegenerative diseases. Using the 6-OHDA induced rat Parkinsonian model, we examined if calretinin (CR), one of CaBP family, could play the similar role in the Parkinson's disease because CR is profusely localized in dopaminergic neurons of the substantia nigra pars compacta (SNPC) of the rat. Employing immunohistochemical analyses, we found that the survival rate of CR neurons was significantly higher than that of tyrosine hydroxylase (TH) neurons in the SNPC of the Parkinsonian rat. Furthermore double-labeled fluorescent microscopy revealed that almost all surviving TH neurons were also positive to CR. Our data suggest that CR-positive neurons are less vulnerable to 6-OHDA and CR in the dopaminergic neurons may have a protective function for survival of these neurons in the experimentally induced Parkinsonian rat.
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PMID:Relative sparing of calretinin containing neurons in the substantia nigra of 6-OHDA treated rat parkinsonian model. 1065 Jan 44

Double-immunolabelling experiments for the combinations, calretinin (CR)-calbindin, CR-tyrosine hydroxylase (TH) and calbindin-TH, were performed in rhesus monkeys to compare the chemical organization of the nucleus accumbens (ACC) in primates and rodents. Additionally, the soma sizes and numbers of primary dendrites of cholinergic neurons in the subregions of ACC were compared with those of caudate-putamen. Our findings subserve the shell-core concept also in the primate ACC, as like in the rat, CR immunoreactivity (-ir) due to intense neuropil labelling is very strong in the shell of rhesus monkey, but poor in the core. The staining intensity of this marker decreases in dorsoventral direction. An almost complementary pattern was noted in sections of the monkey ACC immunostained for both calbindin and TH. The cholinergic interneurons of the nucleus caudatus-putamen are clearly distinguished from those of the ACC and insula Calleja magna by their much bigger soma sizes and higher numbers of primary dendrites. Cholinergic neurons of the shell were found to be slightly, but significantly, larger than those of the core that also subserves subdivision of the primate ACC into shell and core. A low proportion of tyrosine-hydroxylase-immunostained cells, already previously described below the rostral ACC, co-expressed CR but not calbindin. A CR-immunoreactive neuronal population, intermingled with these cells, extends as a stripe medially to the ACC along the septal part of corpus callosum into the lateral septal area. The presumed origin of CR-immunoreactive fibres in the shell of ACC is discussed.
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PMID:The core-shell dichotomy of nucleus accumbens in the rhesus monkey as revealed by double-immunofluorescence and morphology of cholinergic interneurons. 1070 Jun 8

This paper re-examines a previously published segmental map of the frog diencephalon (Puelles et al. [1996] Brain Behav.Evol. 47:279-310) by means of immunocytochemical mapping of calretinin, calbindin, and tyrosine hydroxylase. The distribution of neuronal populations, axon tracts, and neuropils immunoreactive for these markers was studied in adult specimens of Rana perezi and Xenopus laevis sectioned sagittally or horizontally. Emphasis was placed on study of the relationship of observed chemoarchitectural boundaries with the postulated overall prosomeric organization and the schema of nuclear subdivisions we reported previously, based on acetylcholinesterase histochemistry and Nissl pattern in Rana. The data reveal a large-scale correspondence with the segmental map in both species, although some differences were noted between Rana and Xenopus. Notably, retinorecipient neuropils were generally immunoreactive for calretinin only in Rana. Importantly, calretinin immunostaining underlines particularly well the transverse prosomeric boundaries of the dorsal thalamus. A number of nuclear subdivisions noted before with AChE were corroborated, and some novel subdivisions became apparent, particularly in the anterior nucleus of the dorsal thalamus and in the habenular complex. The mapping of tyrosine hydroxylase clarified the segmental distribution of the catecholaminergic cell groups in the frog forebrain, which is comparable to that observed in other vertebrates.
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PMID:Patterns of calretinin, calbindin, and tyrosine-hydroxylase expression are consistent with the prosomeric map of the frog diencephalon. 1071 42


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