Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 42-year-old female with clinical and endocrine indications of Cushing's syndrome, as well as periodic hypertension and increased urinary catecholamines and their metabolites, benefitted from removal of a pheochromocytoma. Adrenocortical hyperplasia was present. Electron microscopy showed catecholamine-type granules in the tumor cells; in addition, immunoreactive ACTH, leu-enkephalin, somatostatin, and serotonin were identified. Such studies were performed for the first time in this unusual condition.
 ...
PMID:Pheochromocytoma producing immunoreactive ACTH with Cushing's syndrome. 609 99

The plasma levels of somatostatin (SRIF) were studied in normal subjects and patients with various disorders by a sensitive and specific radioimmunoassay. In 45 normal subjects, the fasting plasma SRIF concentrations were 13.3 +/- 5.3 pg/ml (mean +/- SD). Very high concentrations of plasma SRIF, ranging from 125.0 pg/ml to 400.0 pg/ml, were found in all four patients with medullary carcinoma of the thyroid examined and the SRIF levels were changed in parallel with their clinical course after resection of the tumor. A case of pheochromocytoma also showed a relatively high SRIF concentration in plasma (47.0 pg/ml), but the plasma SRIF level decreased to 8.7 pg/ml after removal of the tumor. In normal subjects, plasma SRIF levels did not fluctuate during 2 hr-observation period in basal state. Glucagon (1 mg, iv) and secretin (3 CHRU/kg B.W., iv infusion over 30 min) had no effect on the SRIF levels in the peripheral blood plasma of normal subjects. On intravenous infusion of arginine (0.5 g/kg B.W.) over 30 min, all 6 normal subjects showed a significant increase in plasma SRIF 30-45 min after the start of the infusion (basal value, 11.6 +/- 1.5 pg/ml; peak value, 27.2 +/- 3.0 pg/ml; p less than 0.005). Two cases of medullary thyroid carcinoma showed exaggerated responses after the arginine administration (increases of 103 pg/ml and 157 pg/ml, respectively), suggesting that SRIF was released from the tumor. The findings indicate that plasma SRIF determination in the basal state and after arginine administration is useful for detecting and following up SRIF-producing tumors.
 ...
PMID:Plasma somatostatin in normal subjects and in various diseases: increased levels in somatostatin-producing tumors. 612 47

An adrenal pheochromocytoma producing somatostatin (SRIF) and vasoactive intestinal polypeptide (VIP) in a 17-year-old boy is presented. High concentrations of immunoreactive (IR)-SRIF were found in plasma taken from the antecubital vein (31.0-33.0 pg/ml) and the inferior caval vein near the tumor (54.6 pg/ml), but after removal of the tumor the values became normal (11.0-15.2 pg/ml). In two portions of the resected tumor, considerable but different amounts of IR-SRIF (151.7 and 12.1 ng/g wet wt) and IR-VIP (13.0 and 5.5 ng/g wet wt) were demonstrated with size heterogeneities. Immunohistochemically, many IR-SRIF cells and a few IR-VIP cells were observed, but no cell reacting with both anti-SRIF and anti-VIP sera was found. Electronmicroscopically, many tumor cells had catecholamine-like granules (250-350 nm in diameter) while some others had VIP-like granules (110-140 nm in diameter). However, no granules resembling the SRIF granules seen in the pancreatic D cells were found. This seems to be the first report of an adrenal pheochromocytoma that produces SRIF and VIP simultaneously. It provides information on the histogenesis of hormone-producing neurogenic tumors.
 ...
PMID:Immunoreactive somatostatin and vasoactive intestinal polypeptide in adrenal pheochromocytoma. An immunochemical and ultrastructural study. 613 78

The concentration of epinephrine, norepinephrine, dopamine, met-enkephalin-, ACTH-, calcitonin- and somatostatin-like immunoreactivity (IR) were determined in the extracts of 9 adrenal pheochromocytomas from 7 patients. Six of these patients had Sipple's syndrome. There was a close correlation between the amounts of met-enkephalin-IR and of epinephrine present in the tumor tissue (p less than 0.01). Such a correlation was not found between catecholamines and the other polypeptide hormones investigated. The relevance of the close parallel in the occurrence of met-enkephalin-IR and epinephrine in human adrenal pheochromocytoma tissue is unknown, but it underlines earlier observations in the normal bovine and rat adrenal medulla on a co-storage and co-release of these substances in normal circumstances.
 ...
PMID:A close correlation between the amount of met-enkephalin-immunoreactivity and epinephrine in adrenal pheochromocytoma tissue from patients with Sipple's syndrome. 614 10

Somatostatin (SRIF)-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in sympathetic nerves and ganglia and in adrenal medullary cells. Studies were therefore performed to determine whether SRIF-LI was present in an adrenal pheochromocytoma. Acetic cid extracts of pheochromocytoma tissue contained high SRIF-LI concentrations (5.52 micrograms/g wet wt). On Sephadex G-75 gel filtration, the major peak of pheochromocytoma SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the tumor. Pheochromocytoma SRIF-LI coeluted with synthetic SRIF on reverse phase high pressure liquid chromatography. Pheochromocytoma SRIF-LI purified by high pressure liquid chromatography was equipotent to synthetic SRIF in inhibiting (Bu)2cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in the patient before surgery and was restored toward normal after removal of the tumor. Serum levels of GH, TSH, and insulin were not obviously different before and after tumor removal. The results indicate that SRIF-LI is produced in excessive quantities by a pheochromocytoma. The immunological, chromatographic, and biological properties of the pheochromocytoma SRIF-LI suggest that it is indistinguishable from synthetic SRIF. This finding extends the list of peptides produced by pheochromocytoma and may provide an additional serum marker for the tumor in man.U
 ...
PMID:Somatostatin-like immunoactivity and biological activity is present in a human pheochromocytoma. 684 67

The increased understanding of the neuroendocrine tumors at a cellular and molecular level has led to the development of new radiopharmaceuticals for imaging. Two of the imaging agents include 131I metaiodobenzylguanidine (131I-MIBG) and 111In-DTPA-D-Phe1-octreotide (111In-pentetreotide) each having specific localization in certain neuroendocrine tumors. The selective uptake of these radiopharmaceuticals by the tumor cells has generated interest in potential use for targeted radiotherapy for neuroendocrine tumors. 131I-MIBG has been used to treat patients with pheochromocytoma, neuroblastoma, carcinoid tumors, medullary thyroid carcinoma, and paragangliomas. The tumor responses have been variable with the most encouraging results being in patients with pheochromocytoma. The dose-limiting toxicity has been thrombocytopenia or granulocytopenia. 111In-pentetreotide has been used as therapy in only a few patients and has resulted in objective evidence of tumor responses. A therapeutic agent using a somatostatin analogue will most likely require radiolabeling with a beta- or possibly an alpha-emitting radionuclide to achieve significant and durable tumor responses.
 ...
PMID:Therapy of neuroendocrine tumors with radiolabeled MIBG and somatostatin analogues. 757 46

An account is given of the results observed with I-131 MIBG scintigraphy in four patients (1 bladder pheochromocytoma, 3 neuroblastomas) chosen on account of their particular clinical and diagnostic interest from a series of 41 apudoma patients examined by means of this technique. In the first patient, the unusual site of the tumor in the posterior wall of the bladder meant that its detection by I-131 MIBG was only possible after catheterization of the bladder. In the second patient, uptake in the metastasis was only evident after removal of the primary tumor. In the third patient, the scintiscan revealed several metastases (some in bone) not detected by CT. In the fourth patient (congenital neuroblastoma), enhanced uptake accompanied the appearance of high plasma catecholamine and urinary vanillylhandelic acid values, suggesting a functional switch from a nonsecreting to a secreting form. a supplementary In-111 DTPA-Octreotide (OCT) scintiscan of this patient demonstrated the presence of somatostatin receptors on the neuroblasts. Thus, this examination would seem particularly useful for the differentiation of nonsecreting neuroblastomas. Its employment in assessment of the therapeutic capacity of OCT itself is also suggested.
 ...
PMID:I-131 MIBG scintigraphy of neuroectodermal tumors. Comparison between I-131 MIBG and In-111 DTPA-octreotide. 775 Feb 19

In-111 pentetreotide scintigraphy of 10 patients with residual or metastatic medullary thyroid carcinoma is described. Six patients had sporadic tumor and 4 had MEN IIB. Foci of increased tracer uptake were observed in 9 patients: in the thyroid bed (4 patients), the mediastinum (3 patients.), the shoulder area and left lower abdomen (1 patient), and the left upper abdomen (1 patient). The 10th patient had no abnormal uptake. CT confirmed 2 mediastinal lesions and 2 out of 3 thyroid masses, but did not detect the thyroid remnants or the lesions in the shoulder area and abdomen. Lung lesions < or = 1 cm in diameter and ill-defined liver foci (2 patients) were seen on CT, but not on scintigraphy. Small liver metastases not demonstrated on CT or on scintigraphy were identified at surgery in a MEN IIB patient. Elevated urinary epinephrine was found in 2 out of 4 MEN IIB patients. In one, tracer uptake in the left adrenal corresponded to a mass on CT, to pathological uptake of MIBG and DMSA, and to a tumor removed at surgery. The second patient had peritoneal spread of malignant pheochromocytoma (at surgery), but negative CT and only a single focus in the left lower abdomen on scintigraphy. Somatostatin-receptor imaging is useful for the detection of residual and recurrent medullary thyroid carcinoma, and may identify pheochromocytoma in MEN IIB patients.
 ...
PMID:Somatostatin-receptor imaging of medullary thyroid carcinoma. 791 71

The somatostatin (SS) gene is transcriptionally regulated via the cyclic AMP (cAMP) response element (CRE), located in the proximal promoter (-41 to -48 bp). We have previously reported that glucocorticoids induce dose-dependent cell-specific alterations in the steady-state SS mRNA level. Here we have investigated direct transcriptional control of the SS gene by glucocorticoids. We have examined transcriptional interaction between glucocorticoids and the cAMP signalling pathway and mapped the 5' upstream regulatory region of the SS gene involved in glucocorticoid transactivation. Transcriptional regulation was determined by analysis of chloramphenicol acetyltransferase (CAT) activity in PC12 rat pheochromocytoma cells and A126-1B2 (protein kinase A-deficient mutant PC12) cells, by acute transfection of 5' flanking SS DNA (- 750, -250 and -71 bp) ligated to the reporter (CAT) gene. Dexamethasone (DEX) induced a dose-dependent 2.2-fold stimulation of SS gene transcription in PC12 cells, but not in A126-1B2 cells. Other steroid and thyroid hormones tested, and retinoic acid, were ineffective, while cAMP and forskolin stimulated gene transcription 4-5-fold in PC12 cells but not in A126-1B2 cells. DEX exerted an additive effect on cAMP-induced gene transcription. Deletion of the promoter from -750 to -71 bp (but not from -750 to -250 bp) abolished all stimulatory effects of DEX without affecting cAMP responsiveness. Mutation of the CRE abrogated both DEX- and cAMP-dependent gene enhancement. Gel electrophoretic mobility shift assays confirmed that the -250 to -71 bp region of the SS promoter (but not the -71 to +55 bp domain) binds specifically to a glucocorticoid response element-sensitive nuclear protein(s) from PC12 cells, suggesting a putative glucocorticoid receptor interaction with SS promoter DNA. We conclude that glucocorticoids regulate SS gene transcription positively. Glucocorticoid-induced transactivation shows dependence on protein kinase. A activity, and may be mediated via protein-protein interaction between the glucocorticoid receptor and the CRE binding protein. DNA sequences upstream from the CRE between -250 and -71 bp in the SS promoter appear to be the target of glucocorticoid action.
 ...
PMID:Glucocorticoids activate somatostatin gene transcription through co-operative interaction with the cyclic AMP signalling pathway. 791 2

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide-containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target-specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasoconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene-related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstriction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increases during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
 ...
PMID:Neuropeptides in the sympathetic system: presence, plasticity, modulation, and implications. 802 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>