Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cortical GABAergic neurons are generated in the ventral telencephalon and migrate dorsally into the cortex following a tangential path. GDNF signaling via GFRalpha1 was found to promote the differentiation of ventral precursors into GABAergic cells, enhancing their neuronal morphology and motility. GDNF stimulated axonal growth in cortical GABAergic neurons and acted as a potent chemoattractant of GABAergic cells. These effects required GFRalpha1 but neither RET nor NCAM, the two transmembrane signaling receptors known for GDNF. Mutant mice lacking GDNF or GFRalpha1, but neither RET nor NCAM, showed reduced numbers of GABAergic cells in the cerebral cortex and hippocampus. We conclude that one of the normal functions of GDNF signaling via GFRalpha1 in the developing brain is to promote the differentiation and migration of cortical GABAergic neurons. The lack of involvement of RET or NCAM in these processes suggests the existence of additional transmembrane effectors for GDNF.
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PMID:GDNF and GFRalpha1 promote differentiation and tangential migration of cortical GABAergic neurons. 1574 46

Glial-cell-line-derived neurotrophic factor (GDNF) exerts its effect through a multi-component receptor system consisting of GFRalpha1, RET and NCAM. Two highly homologous alternatively spliced GFRalpha1 isoforms (GFRalpha1a and GFRalpha1b) have previously been identified. In this study, isoform specific real-time PCR assays were used to quantify the expression levels of GFRalpha1, RET and NCAM isoforms in murine embryonic and adult tissues. The expression levels of GFRalpha1b were found to be comparable to that of GFRalpha1a in peripheral tissues. However, GFRalpha1a was the predominant isoform expressed in the whole brain. The co-expressions of GFRalpha1 and the co-receptors were developmentally regulated and differentially expressed in some tissues. Microarray analyses of GFRalpha1 isoforms transfected cells stimulated with NTN showed distinct and non-overlapping gene profiles. These observations are consistent with the emerging view that the combinatorial interactions of the spliced isoforms of GFRalpha, RET and NCAM may contribute to the pleiotropic biological responses.
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PMID:Tissue expression of alternatively spliced GFRalpha1, NCAM and RET isoforms and the distinct functional consequence of ligand-induced activation of GFRalpha1 isoforms. 1597

We report on the first case of benign perineurially differentiated peripheral nerve sheath tumor (perineurioma) presenting as a bleeding gastric mass in a 30-year-old, previously healthy woman with no signs or stigmata of von Recklinghausen's disease or other primary tumor at time of presentation. Gastric resection specimen revealed an ulcerated moderately cellular mesenchymal tumor consisting of elongated wavy spindle cells arranged in a fascicular and sheet-like pattern with focal whorling and occasional alternation of dark staining cellular and light staining hypocellular areas. Tumor cells were strongly immunoreactive for epithelial membrane antigen, CD56 (N-CAM), and vimentin, but were negative for S-100-protein and other lineage-specific epithelial, mesenchymal, hematolymphoid, and reticulo-histiocytic markers. CD117 revealed numerous positive staining mast cells, but the lesional cells were not reacting. We presume that the combined histological and immunohistochemical profiles of this unusual gastric neoplasm are consistent with a diagnosis of perineurioma with a probably benign biological behavior. To our knowledge, this is the first report of gastric perineurioma, an extremely rare mesenchymal lesion that should be considered among the differential diagnoses of gastrointestinal stromal tumor, especially the so-called KIT-negative GIST. Gastrointestinal perineuriomas might be under-recognized, as our case was initially diagnosed as a benign GIST.
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PMID:Perineurioma of the stomach. A rare spindle cell neoplasm that should be distinguished from gastrointestinal stromal tumor. 1613 53

We reported a case of intravascular T-cell lymphoma (T-IVL) with anaplastic large cell morphology, the hemophagocytic syndrome, and an aggressive clinical course. Phenotypic analysis of the tumor cells revealed CD2+, CD3-, CD4+, CD5-, CD8-, CD30+, CD56-, T-cell receptor alpha/beta-, ALK-, TIA1+, granzyme B+, and perforin+. No association with Epstein-Barr virus was found by in situ hybridization. A review revealed that 25 cases of T-IVL have been reported in the available literature, only two of which were of CD30+ anaplastic large cell or cytotoxic T-cell type. The findings in the present case may highlight the unique clinicopathologic aspects of a subset of CD30-positive T-IVLs with an ALK-negative cytotoxic phenotype.
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PMID:Intravascular large T-cell lymphoma: a case report of CD30-positive and ALK-negative anaplastic type with cytotoxic molecule expression. 1618

Neurturin (NRTN), artemin (ARTN), persephin (PSPN) and glial cell line-derived neurotrophic factor (GDNF) form a group of neurotrophic factors, also known as the GDNF family ligands (GFLs). They signal through a receptor complex composed of a high-affinity ligand binding subunit, postulated ligand specific, and a common membrane-bound tyrosine kinase RET. Recently, also NCAM has been identified as an alternative signaling receptor. GFLs have been reported to promote survival of cultured dopaminergic neurons. In addition, GDNF treatments have been shown to increase morphological differentiation of tyrosine hydroxylase immunoreactive (TH-ir) neurons. The present comparative study investigated the dose-dependent effects of GFLs on survival and morphological differentiation of TH-ir neurons in primary cultures of E14 rat ventral mesencephalon. Both NRTN and ARTN chronically administered for 5 days significantly increased survival and morphological differentiation of TH-ir cells at all doses investigated [0.1-100 ng/ml], whereas PSPN was found to be slightly less potent with effects on TH-ir cell numbers and morphology at 1.6-100 ng/ml and 6.3-100 ng/ml, respectively. In conclusion, our findings identify NRTN, ARTN and PSPN as potent neurotrophic factors that may play an important role in the structural development and plasticity of ventral mesencephalic dopaminergic neurons.
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PMID:The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons. 1632 3

A 67-year-old woman was admitted with impaired general performance, suffering from fatigue, chest oppression on exertion, and paresthesia of the finger trips. The laboratory findings showed increased white blood cells with abnormal cells, and serum immunofixation test showed monoclonal IgM kappa paraprotein. On flow cytometric immunophenotyping with CD38 gating, most of the abnormal cells expressed surface CD20, CD138, cytoplasmic IgM, but neither surface CD56 nor surface IgM. Immunohistochemical staining of abnormal cells was positive for surface CD38, surface CD20 and cytoplasmic IgM. The final diagnosis was plasma cell leukemia IgM kappa type. Electrocardiography (ECG) on admission showed ST depression in II, III, aV(F), V4, V5, and V6. Coronary angiography (CAG) is invasive and difficult for patients with renal failure, therefore the patient underwent transthoracic Doppler echocardiography (TTDE), which revealed reduced coronary flow velocity reserve (CFVR). Two courses of VAD therapy were administered, then the condition improved, the serum IgM level decreased, abnormal cells were decreased in peripheral blood and bone marrow aspirates, and the creatinine levels improved. With the return of normal ECG findings and improved CFVR, the abnormal ECG and reduction in CFVR was thought to be associated with the hyperviscosity syndrome in PCL. Noninvasive assessment of CFVR by TTDE is significantly useful for the patients who have renal failure and need chemotherapy.
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PMID:[Effective measurement of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography (TTDE) for plasma cell leukemia with hyperviscosity syndrome]. 1647 78

We describe a case of primary neuroendocrine carcinoma arising from the anterior vaginal wall of a 67-year-old woman. Primary neuroendocrine carcinoma of the vagina is a rare entity with only 25 previously reported cases in the literature. In previous reports, these tumors have not been distinguished from primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma). The tumor was composed of cells that showed neuroendocrine-type nuclear features with hyperchromasia, nuclear molding, occasional small nucleoli, and a chromatin pattern that was finely granular. The tumor cells were positive for cytokeratin 20 (CK20), neuron specific enolase, pancytokeratin, epithelial membrane antigen, and chromogranin A expression. Ki-67, a marker of proliferation, was also positive in>90% of cells. The tumor cells showed intense expression of Bcl-2 oncoprotein and mild to moderate expression of c-KIT. Synaptophysin, neurofilament, CD45, CD56, CD10, S-100, HMB-45, cytokeratin 7, and thyroid transcription factor 1 were negative. This pattern of staining is consistent with a Merkel cell carcinoma. This is the first report of a primary neuroendocrine carcinoma of the vagina with a Merkel cell phenotype. Previous studies have not distinguished primary neuroendocrine carcinoma of the vagina from Merkel cell carcinoma of the skin. Positive expression of CK20 in primary small cell carcinoma of the vagina might represent a Merkel cell carcinoma subtype of this tumor.
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PMID:Primary neuroendocrine carcinoma of the vagina with Merkel cell carcinoma phenotype. 1653 63

Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).
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PMID:Small cell carcinoma of the prostate: an immunohistochemical study. 1672 47

Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating PSA-NCAM(+) and Doublecortin(+) neural precursors within the RMS and OB, and Neu-N(+) mature neurons in the OB. This work demonstrates that in vivo cell labeling of progenitor cells for MRI is possible and enables the serial, non-invasive visualization of endogenous progenitor/precursor cell migration.
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PMID:Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain. 1681 67

Interactions between the neural cell adhesion molecules NCAM and N-cadherin with the fibroblast growth factor receptor (FGFR) are important for a number of developmental events and have also been implicated in tumor progression. The factors regulating these interactions are not known. We have used co-immunoprecipitation and co-clustering paradigms to show that both adhesion molecules can interact with the 3Ig IIIC isoform of the FGFR1 in a number of cell types. Interestingly, whereas the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. We also demonstrate for the first time that all of the major isoforms of NCAM can interact with the FGFR. Using deletion mutagenesis we have found that the adhesion molecule/FGFR interaction can withstand the removal of most of any one of the FGFR immunoglobulin-like domains (D1-D3). In contrast, the FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif that can be found in the linker region between D1 and D2. As this motif can be spliced out of all four FGFRs, it suggests that this is one mechanism that can regulate the interaction of the receptor with different ligand classes.
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PMID:The fibroblast growth factor receptor acid box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule. 1700 51


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