Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop.
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PMID:Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach. 352 38

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.
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PMID:Establishment and characterization of a neuroendocrine skin carcinoma cell line. 354 33

Four cases of esophageal carcinoma arising in metaplastic Barrett's epithelium are presented in which multidirectional differentiation was demonstrated by light and/or electron microscopy and immunohistochemistry. All tumors and adjacent mucosa produced both neutral and acidic mucins, as well as one or more hormones indigenous to the gut, including gastrin, bombesin, substance P, somatostatin, and serotonin. Gastrin and somatostatin were the peptides most frequently identified in the tumors, while somatostatin and serotonin predominated in Barrett's epithelium. Ultrastructurally, neurosecretory-type granules, 80-250 nm in diameter, were present in 2 cases; squamous features also were present in one of these cases. One patient displayed hypertrophic osteoarthropathy, which disappeared after the tumor was resected. These cases represent the majority of the Barrett-associated carcinomas in our material. Compared to the "pure" esophageal adenocarcinomas not included in this report, these tumors behaved more aggressively, with wider local involvement and nodal and systemic metastases at the time of presentation. The incidence of multidifferentiation in esophageal carcinomas is not known nor is its possible significance, particularly with regard to tumors arising in metaplastic epithelium. This group may merit further study to detect true differences, if any, between these esophageal carcinomas and their apparently more common counterparts.
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PMID:Carcinoma with multidirectional differentiation arising in Barrett's esophagus. 613 8

Two cases of gastrin releasing peptide (GRP)-producing medullary thyroid carcinoma are presented. Immunohistochemical examination revealed the presence of GRP-like immunoreactivity (IR-GRP) in the primary tumor tissues. High concentration of IR-GRP was also demonstrated in extracts of the primary tumors by radioimmunologic means with use of a GRP-specific antiserum. Chromatographic analysis showed that the immunoreactivity was composed of at least two molecular forms: one behaved as synthetic porcine GRP on Sephadex G-50 gel filtration and the other as porcine GRP (14-27), a C-terminal active fragment of GRP. The IR-GRP was shown not to be attributed to bombesin-like immunoreactivity. Substance P-like immunoreactivity was not detected in the tumor tissues by either immunohistochemical or radioimmunologic means. This is, as far as the authors are aware, the first finding of IR-GRP as an ectopic product in medullary carcinoma.
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PMID:Gastrin-releasing peptide immunoreactivity in medullary thyroid carcinoma. 637 Apr 16

Nine cases of endocrine carcinoma, intermediate-cell type of the uterine cervix, were found in a study of 404 cases listed in the files of the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston as adenocarcinoma of the cervix. Based on light microscopic patterns, these cases were divided into pure endocrine carcinoma (six cases), and endocrine carcinoma mixed with adenocarcinoma (three cases). All tumors were 3 cm or larger in at least one dimension. On light microscopic examination, the predominant pattern was trabecular; however, insular, glandular, and spindle patterns were also identified. Argyrophilic granules were demonstrated in all cases by Grimelius stain, and Fontana-Masson (argentaffin) stain was negative. Electron microscopic examination of three cases showed membrane-bound, dense-core granules of the neurosecretory type. Although no endocrine symptoms were found, immunoperoxidase studies demonstrated 5-hydroxytryptamine in seven cases, substance P in three, vasointestinal polypeptide in two, pancreatic polypeptide in one, and somatostatin in one. Clinical behavior of these tumors was extremely aggressive. Although five cases were Stage IB at presentation, two Stage IIB, one Stage IIIB, and one Stage IV, 87.5% of these patients died of their neoplasms within 3 years. This study emphasizes the importance of correctly diagnosing endocrine carcinoma, intermediate-cell type in the uterine cervix, because of the poor prognosis of this tumor when compared with adenocarcinoma of the cervix.
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PMID:Endocrine carcinoma intermediate cell type of the uterine cervix. 638 96

Achalasia is a disease of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter, resulting in obstruction. Aperistalsis and dilation of the esophageal body occurs later, contributing to the esophageal dysfunction. Gastrointestinal bleeding in achalasia is an infrequent complication usually caused by stasis ulcer, esophageal varices, carcinoma, or pneumatic dilation of the sphincter. We describe here a patient with longstanding achalasia who bled vigorously from a proximal esophageal site that can be identified as arterial bleeding by endoscopy. Subsequent esophageal resection allowed detailed histological and immunohistochemical examination, which revealed a vascular ectasia. This lesion was associated with an unusually rich network of nerve fibers containing calcitonin gene-related peptide. Neuropeptide Y- and substance P-containing fibers were found to be decreased in this lesion as compared with controls. On the other hand vasoactive intestinal peptide- and nitric oxide synthase-containing fibers appeared quantitatively similar to those of controls. Calcitonin gene-related peptide is known to be involved in angiogenesis and may have played a causative role in the development of this lesion. Vascular ectasia may represent a hitherto unreported complication of achalasia.
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PMID:Innervation of an esophageal ectatic submucosal blood vessel in achalasia and a comparison with normals. 752 10

Baseline and agonist-stimulated secretion of fucose, hexose, and protein (markers of mucus secretion) was investigated in vitro in 45 bronchial segments from 14 patients with cystic fibrosis (CF) (three after heart-lung transplant, the remainder < 4.5 h after autopsy), in 51 segments from 26 patients with carcinoma (24 resection, 2 after autopsy), and in 4 segments from 3 patients with bronchiectasis (resection). Basal rates of secretion of each mucus marker by CF bronchi were not significantly different from those by carcinoma bronchi bronchiectatic bronchi. However, rates of secretion of each marker in response to the cholinomimetic methacholine (10 microM; n = 11-18, depending on marker) and the beta 2-adrenoceptor agonist terbutaline (10 microM; n = 9-11) were significantly (p < .05) increased in carcinoma bronchi (by 50-117% above basal), but not in CF airways (n = 11-14). The secretory response to the sensory neuropeptide substance P (1 nM to 10 microM; n = 5-7) was also reduced in CF compared with carcinoma bronchi. Physiological and morphological data indicated that the reduced response by CF tissue could not be accounted for by inclusion of autopsy tissue in the study. These data suggest a defect in autonomic control of bronchial secretion in CF, not in the basal rate of secretion, but in its response to receptor stimulation.
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PMID:Impaired stimulus-evoked mucus secretion in cystic fibrosis bronchi. 767 87

Sixty-four kinds of cell lines were examined as to their ability to degrade glucagon using conditioned-media obtained from their protein-free cultures. Two human tumor cell lines were shown to produce this activity, and the cell line, HPC-YO, established from a human pancreatic carcinoma was shown to produce the highest level of activity. The glucagon-degrading enzyme (GDE) was purified from HPC-YO conditioned-medium by a combination of ion-exchange, gel filtration, and hydroxylapatite column chromatographies. The purified GDE also degraded vasoactive intestinal polypeptide (VIP) and secretin, however, it did not cleave EGF, gastrin, insulin, somatostatin, substance P, neurotensin, or growth hormone. The molecular weight of GDE is 83,000, as determined on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of GDE was blocked, and the five partial amino acid sequences obtained on lysyl-endopeptidase digestion were determined to be N-L-T-E-E-Y-D-V-S-D-G-E-I-E-L-L-Y-E-K, V-E-T-Y-Y-D-L-L-F-E-K, L-Y-W-F-L-D-E-A-K, S-N-S-T-S-Y-V-K, and Y-Y-A-S-T-S-Y-D-D-T-Y-K. The same or homologous amino acid sequences have not been found in known proteins, demonstrating that GDE is a novel peptidase that degrades the secretin family: glucagon, VIP, and secretin.
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PMID:A novel proteinase, glucagon-degrading enzyme, secreted by a human pancreatic cancer cell line, HPC-YO. 777 1

The innervation of the sphincter of Oddi (SO) has been extensively studied experimentally, but human studies have not been published, which is why this study was undertaken. Biopsies, taken by gastroscopy-biopsy forceps from duodenal epithelium of the papilla of Vater and from ampullary epithelium after sphincterotomy, did not demonstrate nerves and could not be used for studying SO innervation. Therefore SO specimens were obtained from brain-dead organ donors (N = 5) and from autopsies (N = 14). By staining with a myelin marker S-100, a rich network of nerves was demonstrated in SO. The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI) (or its immunologically similar human equivalent peptide histidine methioninamide, PHM), neuropeptide Y, calcitonin gene-related peptide (CGRP), galanin, substance P, enkephalin, bombesin, and somatostatin were studied by immunohistochemical technique. SO demonstrated immunoreactivity for VIP, PHI (PHM), neuropeptide Y, CGRP, galanin, somatostatin, substance P, and enkephalin, but no immunoreactivity was observed for bombesin. The SO immunoreactivity was similar in specimens from organ donors and from autopsies of victims of violence without pancreatobiliary diseases (N = 3) when the specimens were taken within 48 hr of death. Autopsy specimens of SO from subjects with gallstone disease (N = 5), recurrent pancreatitis (N = 3) or periampullary carcinoma (N = 3) also demonstrated similar immunoreactivity. We conclude that VIP-, PHI- (PHM-), neuropeptide Y-, CGRP-, galanin-, substance P-, somatostatin-, and enkephalin-like immunoreactivity occur in human SO. These neuropeptides may have role in the neural control of human SO function.
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PMID:Peptidergic innervation of human sphincter of Oddi. 831 11

We treated a 65 year-old man with severe facial pain after extended maxillectomy due to carcinoma of maxillar sinus. He had been suffering from pain at rest, on mastication, or at treatment of surgical wound. Various kinds of analgesics had been tried, but his pain did not disappear. At 17 weeks after the operation, he came to our pain clinic. Because his pain was thought to be due to reflex sympathetic dystrophy (RSD), stellate ganglion blocks (SGB) were performed. After 5 administrations of SGB, pain was reduced markedly but the pain at treatment of wound persisted. We thought that persistent pain would need trigeminal nerve block. Then Gasserian ganglion block was performed directly through an open wound after the operation. After the Gasserian ganglion block, the pain was diminished remarkably. He could tolerate procedures for facial prosthesis. Pain control after the operation in this patient was very efficient to improve his quality of life. Serum concentrations of catecholamines, serotonin and substance P were measured. The levels of norepinephrine and serotonin are related to the mechanism of pain as seen in this patient.
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PMID:[Management of severe pain after extended maxillectomy in a patient with carcinoma of the maxillary sinus]. 886 30


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