Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the presence of anterior pituitary hormones; follicle-stimulating hormone (FSH) and its beta-subunit (beta-FSH), luteinizing hormone (LH) and its beta-subunit (beta-LH), beta-subunit of thyroid-stimulating hormone (beta-TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL); the placental hormone human chorionic gonadotropin (hCG); and somatostatin, in paraffin and frozen sections of the human thymus. Epithelial cells in the medulla were immunoreactive for most of these hormones, in varying density and intensity of labeling. The cells labeled varied from epithelial cells surrounding Hassall's corpuscles toward solitary cells or small epithelial aggregates in the medulla. FSH immunoreactivity did occur predominantly in epithelial cells of the cortex, in apparent contrast to the predominant medullary location of cells immunolabeled for beta-FSH. The epithelial nature of FSH-immunoreactive cells was confirmed by two-color immunohistochemistry with anti-keratin antibody. In addition to FSH, some epithelial cells in subcapsule and cortex were labeled by antibodies to beta-FSH, beta-LH, beta-TSH, ACTH, GH, and PRL. Some macrophage-like cells surrounded by a rosette of lymphocytes were immunoreactive for FSH and GH. Some interdigitating reticulum-like cells were labeled by anti-beta-LH. Immunolabeling of lymphocytes was found for hCG, especially lymphocytes in the medulla. Two-color immunohistochemistry with anti-CD3 revealed a strong CD3 expression on hCG-immunoreactive cells, whereas CD3-negative cells were hCG-negative. T cells immunolabeled for hCG were also found in peripheral lymphoid organs.
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PMID:The neural and neuro-endocrine component of the human thymus. II. Hormone immunoreactivity. 139

The mammalian DNA repair enzyme beta-polymerase is encoded by a single-copy gene that is expressed in all tissues and cell lines studied to date. A protein fraction with high binding affinity for an ATF/CREB-like binding element, GTGACGTCAC, at -49 to -40 in the core beta-polymerase promoter has been purified to near-homogeneity from a nuclear extract of bovine testes. The major binding activity, as monitored by gel mobility shift assay, is recovered in 20% yield by a procedure involving oligonucleotide affinity chromatography. The purified protein yields DNase I footprinting and gel shift binding patterns indistinguishable from the activity in crude extracts. The final fraction activates transcription in an in vitro transcription reaction. The native molecular weight of the purified binding activity is about 100-120K as measured by gel filtration. SDS-PAGE of the purified fraction revealed that it contains several polypeptides in the molecular weight range of 30-52K, yet two of these peptides (Mr 49K and 52K) are predominant. Specific binding to the palindrome is salt-sensitive and is consistent with the formation of nine ion pairs (from log KA vs log KCl plots) and has a KA at 200 mM KCl of 5.8 X 10(11) M-1. Kinetic studies with synthetic oligonucleotides as binding ligands indicate that the purified protein can bind tighter to or discriminate between the beta-polymerase ATF/CREB element and similar elements derived from somatostatin and chorionic gonadotropin genes.
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PMID:Mammalian beta-polymerase promoter: large-scale purification and properties of ATF/CREB palindrome binding protein from bovine testes. 182 81

We have investigated the transcriptional activity of human cytomegalovirus, herpes thymidine kinase, human chorionic gonadotropin alpha, somatostatin, immunoglobulin kappa chain, alpha crystallin, albumin and interferon-beta promoters in the fission yeast Schizosaccharomyces pombe. Among these, the human cytomegalovirus, human chorionic gonadotropin alpha, and somatostatin promoters were found to be very active, approximately 11-, 9-, and 0.9-fold as active as the SV40 early promoter, respectively. The remainder of the promoters studied were weak, having only 10-20% of the SV40 promoter activity. Primer extension analysis showed that the strong promoters initiated transcription in S. pombe at the same sites as in mammalian cells, indicating the high similarity between both transcriptional systems.
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PMID:Human chorionic gonadotropin alpha and human cytomegalovirus promoters are extremely active in the fission yeast Schizosaccharomyces pombe. 197 20

The TGACGTCA (CRE) motif required for function by a number of cellular (somatostatin, enkephalin, alpha-human chorionic gonadotropin) and viral (Ad5 E1A-inducible, HTLV-1 TAX-inducible) genes is the site of interaction of multiple sequence-specific complexes. A protocol has been developed for the fractionation and purification of these activities. We report here the purification from HeLa nuclear extracts of a novel 120-kDa polypeptide which by Southwestern blots, gel retardation, and UV cross-linking assays displays CRE-specific binding. The CRE-affinity purified 120-kDa protein displays properties distinct from those of the 43-kDa CREB/ATF polypeptide. The 120-kDa protein is readily phosphorylated in vitro by protein kinase C but not by protein kinase A, suggesting that this molecule may mediate cellular signals distinct from the cAMP-responsive pathway. In vitro transcription-complementation assays utilizing the purified 120-kDa protein failed to transactivate the cAMP-responsive somatostatin promoter suggesting that the mode of action of this 120-kDa polypeptide may require an activation step distinct from the cAMP-signaling pathway.
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PMID:Identification and purification of a novel 120-kDa protein that recognizes the cAMP-responsive element. 213 55

The transcription regulation of many hormone genes is modulated by intracellular second messengers such as cAMP. The cAMP response element binding protein, CREB, binds to the 8 base pair CRE enhancer, TGACGTCA, that is found in the 5'-flank of certain genes including those for somatostatin and the alpha-subunit of human chorionic gonadotropin. The recent characterization of CREB and CREB-related cDNA clones, combined with Southwesterns and Northern blot analyses, reveals a family of transcription factors that dimerize via a leucine zipper motif and bind to the CRE through positively charged basic regions. The CREB cDNA encoding a 327 residue protein is transcriptionally activated via phosphorylation by protein kinases, including the cAMP-dependent protein kinase-A.
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PMID:Characterization of a cAMP-regulated enhancer-binding protein. 214 88

It is well known that carcinoid tumors and some small-cell carcinomas of the lung contain dense-core granules (DCGs). Moreover, a small number of tumors presenting with epidermoid, large-cell, or adenocarcinoma histologic characteristics (so-called atypical endocrine tumors), also contain DCGs. Herein, we describe certain histochemical features of DCG tumors and compare them with other major lung tumor types that lack DCGs (non-DCG tumors). All DCG tumors contained neuron-specific enolase and many contained serotonin. These markers were not present in any non-DCG tumor. Other histochemical markers (glycogen, mucosubstances, corticotropin, beta-human chorionic gonadotropin, keratin, somatostatin, and calcitonin) were found in a proportion of DCG and non-DCG tumors, but were, in general, more common in non-DCG tumors and atypical endocrine tumors than in carcinoids and small-cell carcinomas. alpha-Fetoprotein was rarely found in non-DCG tumors, and was never observed in DCG tumors. The atypical endocrine group represents a class of tumors with a remarkably mixed and varied phenotype. Their potential significance is discussed and methods to facilitate their diagnosis are suggested.
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PMID:Histochemical studies of dense-core granulated tumors of the lung. Neuron-specific enolase as a marker for granulated cells. 240 47

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.
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PMID:Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. 244 25

Among 284 cases of carcinoma of the gallbladder, 21 were identified as undifferentiated carcinoma (UC), with little glandular or other specific epithelial differentiation. These tumors were classified into three histologic types according to the components: (1) small cell type (eight cases); (2) pleomorphic cell type (eight cases); and (3) spindle cell or pseudosarcomatous type (five cases). Histochemical and immunohistochemical study by the immunoperoxidase technique revealed that most of the tumors (13/21) contained mucosubstances, and that all examples of the UC were immunoreactive for epithelial membrane antigen (EMA), keratin, and carcinoembryonic antigen (CEA), thereby indicating the epithelial nature of the neoplastic cells. Vimentin immunoreactivity was found in nine tumors. In 19, the tumor contained various neoplastic endocrine cells, including somatostatin-immunoreactive (14/19), gastrin-immunoreactive (14/19), human chorionic gonadotropin (HCG)-immunoreactive (9/19), pancreatic polypeptide-immunoreactive (4/19), and serotonin-immunoreactive cells (4/19). The prognosis of patients with UC of the gallbladder was poorer than that of patients with differentiated adenocarcinoma.
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PMID:Undifferentiated carcinoma of the gallbladder. A clinicopathologic, histochemical, and immunohistochemical study of 21 patients with a poor prognosis. 245 57

The increased knowledge of the pathobiology of gastrointestinal carcinoid (neuroendocrine) tumours and the improved therapeutic possibilities have brought a demand for more precise diagnosis. Although the carcinoid tumours can often be tentatively recognized in routinely processed microscopic slides, their more accurate identification requires additional diagnostic procedures. General neuroendocrine markers such as the argyrophil reaction of Grimelius and immunohistochemistry with application of antibodies against chromogranin A and of neuron-specific enolase are discriminatory staining methods which are used to reveal the neuroendocrine origin of almost all highly differentiated carcinoid tumours of the gastrointestinal tract. Mid-gut carcinoids, which predominate among these tumours almost unexceptionally contain serotonin. This biogenic amine can be demonstrated by the argentaffin reaction of Masson, serotonin immunoreactively or by formalin-induced fluorescence. The characteristic staining pattern of mid-gut carcinoids is almost invariably preserved in the metastatic deposits and consequently the staining methods for identifying serotonin can also be used on metastases to reveal a primary mid-gut carcinoid. The enterochromaffin-like (ECL) cell carcinoids of the body and fundic area of the stomach often seen in association with pernicious anaemia are argyrophil with the Sevier-Munger silver stain. Other neuroendocrine tumours, viz. antral, duodenal and rectal carcinoids should be studied by a battery of relevant peptide hormone antisera for adequate diagnosis. During the last decade new peptide hormones have been found in circulation in patients with carcinoid tumours, but serotonin and urinary 5-HIAA are still the most important markers for carcinoids of the mid-gut origin. Other clinically useful tumour markers are chromogranin A + B, pancreatic polypeptide, human chorionic gonadotropin alpha and beta subunits. For localizing procedures, angiography is the most reliable investigative method for primary tumours in the gut, whereas CT-scan and ultrasound investigations are good for detection of liver metastases. During the last five years, the therapy for malignant carcinoid tumours has been considerably improved. Chemotherapy has only revealed objective response rates in about 10-30% of the patients giving median survivals from start of therapy of about 10 months. Recently treatment with alpha interferons and the new somatostatin analogue octreotide have given objective responses in 50-75% of patients with malignant mid-gut carcinoid tumours. These patients have now a median survival from start of therapy of 70 months when treated with alpha interferons. In the future new therapies will come into use such as monoclonal antibodies and perhaps also agents blocking different growth factors.
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PMID:Gastrointestinal carcinoid tumours. Histogenetic, histochemical, immunohistochemical, clinical and therapeutic aspects. 266 60

Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells (PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position -60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE), is sufficient to confer cAMP responsiveness to a herpes thymidine kinase/CAT fusion gene. The specific binding of a nuclear protein to the c-fos CRE can be competed by the somatostatin and alpha-chorionic gonadotropin (alpha-CG) promoter regions that contain CREs. Gel mobility shift assays with double-stranded oligonucleotides containing either the wild-type or mutated c-fos CRE sequence have demonstrated that binding occurs only to the wild-type CRE. The nuclear factor binding to the c-fos CRE is likely to be transcription factor CREB (CRE nuclear binding protein), because an affinity-purified 43-kD CREB isolated from PC12 cells binds efficiently in a DNA footprinting assay. Thus, regulation of the c-fos gene transcription appears to involve a mechanism common to many genes that respond to cAMP as a second message leading to cell growth and differentiation.
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PMID:Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. 285 Sep 67


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