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)

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.
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PMID:Calcitonin-secreting tumors of the pancreas: about six cases. 959 18

The intimate, bidirectional link between neuroendocrine and immune systems is now accepted. A modulating effect of the nervous system on immune and inflammatory responses has been corroborated by identification of neuropeptide receptors on immunocompetent cells and the finding that neuropeptides can regulate leukocyte functions. The present study was undertaken to investigate the possible immunomodulatory role of sensory (SOM, CGRP and SP) and autonomic (VIP and NPY) neuropeptides in a murine model of cutaneous leishmaniasis, using two genetically different inbred mouse strains, BALB/c and C57BL/6, respectively susceptible and resistant to Leishmania (L.) major infection. The parameters studied were extent of splenocyte proliferation, as measured by thymidine uptake, and the ability of these cells to secrete IFN-gamma and IL-4 by using a two-site ELISA, upon in vitro challenge with L. major parasites and addition of the neuropeptides. The resistant mouse splenocyte proliferation was enhanced by SOM, CGRP, and VIP at 10(-5), 10(-6) and 10(-9) M concentration, respectively, but was inhibited by NPY at 10(-5) M. Proliferation of the splenocytes from the susceptible strain was inhibited by SOM (10(-11) M) and CGRP(10(-5) M). Somatostatin, at various concentrations, stimulated IFN-gamma secretion in both mouse strain splenocytes, and IL-4 production in the susceptible mouse. Calcitonin gene-related peptide enhanced IFN-gamma secretion in susceptible mouse splenocytes at 10(-6), 10(-7) and 10(-9) M, as did VIP at 10(-10) M and NPY at 10(-7) M. Vasoactive intestinal peptide also stimulated IL-4 production in BALB/c splenocytes at all concentrations used. Substance P had no effect on either cell proliferation or cytokine secretion in either of the two mouse strains. These findings indicate that the nervous system, represented by sensory and autonomic nerve terminals and their content of neuromediators, may be involved in the pathophysiology of cutaneous leishmaniasis.
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PMID:Modulating effects of sensory and autonomic neuropeptides on murine splenocyte proliferation and cytokine secretion induced by Leishmania major. 1046 77

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is important for the control of cardiac dynamics, especially in the conduction system. Our objective was to assess the relative distribution of autonomic nerves in the pig heart, focusing initially on the conduction system but addressing also the myocardium, endocardium and epicardium (see Crick et al. 1999). Quantitative immunohistochemical and histochemical techniques were adopted. All regions of the conduction system possessed a significantly higher relative density of the total neural population immunoreactive for the general neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjacent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventricular node, and the penetrating atrioventricular bundle. A differential pattern of PGP 9.5-immunoreactive innervation was present within the atrioventricular node and between the components of the ventricular conduction tissues, the latter being formed by an intricate network of Purkinje fibres. Numerous ganglion cell bodies were present in the peripheral regions of the sinus node, in the tissues of the atrioventricular groove, and even in the interstices of the compact atrioventricular node. Acetylcholinesterase (AChE)-containing nerves were the dominant subpopulation observed, representing 60-70% of the total pattern of innervation in the nodal tissues and penetrating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most abundant neural subpopulation, representing 37% of the total pattern of innervation in the compact atrioventricular node compared with 25% in the transitional nodal region. A minor population of ganglion cell bodies within the atrioventricular nodal region displayed TH immunoreactivity. The dominant peptidergic nerve supply possessed immunoreactivity for neuropeptide Y (NPY), which displayed a similar pattern of distribution to that of TH-immunoreactive nerve fibres. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves represented 8-9% of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14-19% in the bundle branches. Somatostatin-immunoreactive nerve fibres were relatively sparse (4-13% of total innervation) and were most abundant in the nodes, especially the compact atrioventricular node. The total pattern of innervation of the porcine conduction system was relatively homogeneous. A substantial proportion of nerve fibres innervating the nodal tissues could be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular conduction tissues was similar to that observed in the bovine heart, but markedly different to that of the human heart. It is important that we are aware of these findings in view of the future use of transgenic pig hearts in human xenotransplantation.
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PMID:Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system. 1058 Aug 50

Calcitonin, one of the calcium-regulating hormones, is known to have diverse biological effects including those on the gastrointestinal tract. In this organ, the hormone is reported to inhibit gastric acid secretion, gastric motility, and gastrin secretion and to stimulate release of somatostatin, thereby exerting antiulcer and antilesion effects on stress-induced as well as other types of experimental gastric ulcers or lesions. This fact prompted us to examine changes in serum calcitonin concentration during the development of stress-induced gastric lesions in rats. DA rats were constrained in a stress cage after a 24-h fast and then immersed in 24 degrees C water to the level of the xiphoid process for 2 or 5 h. Serum calcitonin concentrations in stressed rats were significantly lower than those in control rats. To investigate the mechanism of the decline in serum calcitonin level under stress in these rats, we conducted a time-course study of serum calcitonin concentration and ionized calcium level during water-immersion stress, lasting 2 h, and during 4 h following release from the stress. Water immersion caused a remarkable decrease in serum calcitonin concentration as early as at 30 min. After release from stress, serum calcitonin concentration gradually recovered. The ionized calcium level in the blood did not change significantly throughout the experimental period. Furthermore, to examine if the sympathetic nerve system was involved in the stress-induced change of serum calcitonin concentration, alpha- and beta-receptor antagonists were administered intraperitoneally before stress exposure. Administration of alpha-receptor antagonist at a low dose that did not have any effect on serum calcitonin concentration in a preliminary study, restored the decline of serum calcitonin level, whereas beta-receptor antagonist did not. These results suggest that stress-provoked decrease of serum calcitonin concentration may be mediated not by a change of ionized calcium level but by alteration of sympathetic nerve activity (particularly via the alpha-receptor).
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PMID:Changes of serum calcitonin in stress load. 1063 73

The complete thyroid and parathyroid gland removal leads to the abrupt reduction of calcitonin, which can be a factor stimulating growth and intensified activity of APUD system cells in the respiratory tract. Thus, neuroendocrine cells in the lungs and trachea in rats after thyroid and parathyroid removal were evaluated. Paraffin specimens of the examined organs were stained with H+E and impregnated with silver. Calcitonin, synaptophysin, somatostatin, and neuronal-specific enolase were detected immunohistochemically by the use of rabbit specific antibodies. Antibodies used in the study immunostained neuroendocrine cells of the examined organs. Rats with removed thyroid and parathyroid glands presented weakened reaction compared to the control group.
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PMID:Preliminary evaluation of endocrine cells in the rat respiratory tract after thyroid and parathyroid gland removal. 1137 21

Numerous water-electrolyte and hormonal disturbances, including secondary hyperparathyroidism, occur in the course of chronic renal failure. It is assumed that chronic renal failure should affect the activity of C cells in the thyroid gland. Thus, the aim of the study was to evaluate immunohistochemically thyroid C cells in rats with experimental uremia. 30 days after nephrectomy, thyroid fragments were collected from experimental rats. Paraffin embedded sections were stained with H+E and by silver impregnation. Calcitonin (CT), synaptophysin (SY), somatostatin (ST), and neuron-specific enolase (NSE) were detected immunohistochemically in the C cells. A very distinct increase in C cell number in the thyroid and the weakening of majority of examined reactions were observed in rats with experimental uremia.
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PMID:Preliminary evaluation of thyroid C cells in rats with chronic renal failure. 1137 26

1. The ECL cells control gastric acid secretion by mobilizing histamine in response to circulating gastrin. In addition, the ECL cells are thought to operate under nervous control and to be influenced by local inflammatory processes. 2. The purpose of the present study was to monitor histamine mobilization from ECL cells in conscious rats in response to locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators. 3. Microdialysis probes were implanted in the submucosa of the acid-producing part of the rat stomach. Three days later, the agents to be tested were administered via the microdialysis probe and their effects on basal (48 h fast) and stimulated (intravenous infusion of gastrin-17, 3 nmol kg(-1) h(-1)) mobilization of ECL-cell histamine was monitored by continuous measurement of histamine in the perfusate (radioimmunoassay). 4. Locally administered gastrin-17 and sulfated cholecystokinin-8 mobilized histamine as did pituitary adenylate cyclase-activating peptide-27, vasoactive intestinal peptide, peptide YY, met-enkephalin, endothelin and noradrenaline, adrenaline and isoprenaline. 5. While gastrin, sulfated-cholecystokinin-8, met-enkephalin and isoprenaline induced a sustained elevation of the submucosal histamine concentration, endothelin, peptide YY, pituitary adenylate cyclase activating peptide, vasoactive intestinal peptide, noradrenaline and adrenaline induced a transient elevation. 6. Calcitonin gene-related peptide, galanin, somatostatin and the prostanoid misoprostol inhibited gastrin-stimulated histamine mobilization. 7. The gut hormones neurotensin and secretin and the neuropeptides gastrin-releasing peptide, neuropeptide Y and substance P failed to affect ECL-cell histamine mobilization, while motilin and neuromedin U-25 had weak stimulatory effects. Also acetylcholine, carbachol, serotonin and the amino acid neurotransmitters aspartate, gamma-aminobutyric acid, glutamate and glycine were inactive or weakly active as was bradykinin. 8. In summary, a range of circulating hormones, local hormones, catecholamines, neuropeptides and inflammatory mediators participate in controlling the activity of rat stomach ECL cells in situ.
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PMID:ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators. 1173 54

The kidneys are responsible for iodine and of thyroid hormone biodegradation. The aim of this study was the histomorphological and immunohistochemical evaluation of the influence of sex on parafollicular thyroid C cells in rats with chronic renal failure. The experiment included 40 Wistar rats after subtotal nephrectomy, after sham operation, and without any surgical procedure. Two weeks after nephrectomy, fragments of thyroids were collected from the examined animals. Paraffin sections were stained with H+E and by silver impregnation. Calcitonin (CT), synaptophysin (SPh), somatostatin (ST), and neuron-specific enolase (NSE) were detected immunohistochemically in C cells. In rats with experimental uremia, immunostaining for the examined substances increased significantly in comparison to the controls. We also observed higher number of C cells with a stronger reaction in the group of males, compared to the female rats.
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PMID:Thyroid C cells in male and female rats with chronic renal failure. 1205 35

Immunohistochemistry is part of the routine diagnosis of the neuroendocrine tumors. In our study, we included 52 paragangliomas with various localizations by routine histology and immunohistochemistry. In order to increase the diagnostic specificity, a complex immunohistochemistry panel has been performed consisting of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP), somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced antigen retrieval, the immunostaining was performed by StreptABC using DAB as a chromogen. We were the first to demonstrate the presence of Bax and PACAP in paragangliomas. Some of the used markers are of prognostic value. The relationship between Bcl-2 and Bax is decisive in generating the final response to the input apoptotic signals. The Ki-67 antigen staining has gained wide acceptance in prognostic evaluation of other tumor types. We noted a small number of Ki-67 positive cases, which signifies a low mitotic activity of these tumors and a relatively high number of Bax positivities (32.9%) and the much lower number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of paragangliomas.
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PMID:Immunohistochemical features of paragangliomas. 1206 90

Retrograde labeling was combined with cytochemistry to investigate phenotypic differences in primary afferent neurons relaying sensory information from deep and superficial craniofacial tissues. Calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM) immunoreactivity and isolectin IB4, and cholera toxin B (ChTB) binding were examined for trigeminal masticatory muscle and cutaneous afferent neurons. Somata labeled from muscle were larger than cutaneous afferent neurons. Muscle afferent neurons exhibited positive staining as follows: 22% CGRP, 5% SP, 0% SOM; 18% ChTB, 5% IB4. The somata of CGRP- and SP-positive muscle afferent neurons were smaller than that of the overall muscle afferent population. Size differences were not detected between IB4- or ChTB-binding muscle afferent neurons and the total muscle afferent population. The following distribution was found for cutaneous afferent neurons: 26% CGRP, 7% SP, 1% SOM, 26% ChTB, 44% IB4. Cutaneous afferent neurons positive for SP were smaller, while ChTB-binding cutaneous afferents were larger than the overall cutaneous afferent population. No size differences were found between cutaneous CGRP-, SOM-, or IB4-positive neurons and the total cutaneous afferent population. Target-specific differences exist for SOM and IB4. The percentage of cutaneous afferent neurons positive for SOM and IB4 exceeds that for SOM- or IB4-positive muscle afferents. The number of retrogradely labeled neurons never differed between sexes. The percentage of retrogradely labeled muscle afferent neurons that were CGRP-positive was greater in males than females. These data indicate the presence of phenotypic, target, and sex differences in trigeminal ganglion primary afferent neurons.
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PMID:Chemical phenotypes of muscle and cutaneous afferent neurons in the rat trigeminal ganglion. 1268 82


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