Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sandostatin (SMS 201-995 (SMS)), a potent, long acting analog of native somatostatin was used in five patients with functional endocrine tumors (gastrinoma, two patients; insulinoma, one patient; glucagonoma, one, and adult onset nesidioblastosis, one). Primary and secondary peptide levels were obtained during provocation with a test meal, a calcium infusion, a secretin bolus and either a glucagon or tolbutamide bolus. During provocation test, the levels of the primary peptides insulin and C-peptide (nesidioblastosis and insulinoma), gastrin (gastrinoma), glucagon (glucagonoma) and the secondary peptides calcitonin, gastrointestinal peptide, gastrin releasing peptide, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance-P and vasoactive intestinal peptide were obtained at predetermined intervals and quantitated by radioimmunoassay. SMS therapy was begun and peptide levels were again obtained during provocation. SMS suppressed basal primary peptide levels in all patients by more than 50 per cent. In 23 of 26 provocative tests, SMS effectively decreased circulating peptide levels by more than 50 per cent. Thirteen instances of elevated basal secondary peptides were discovered, and SMS universally suppressed these levels by a mean of 54 per cent. Of the 44 provocative tests performed, elevated secondary peptide levels were present in 41. SMS was effective in 31 of these 41 tests. The mean suppression of these provoked secondary peptide levels was 70 per cent. SMS effectively suppresses both basal and provoked peptides and, thus, provides relief of the clinical symptoms induced by pathologic elevations of primary and secondary peptides.
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PMID:Suppression of primary and secondary peptides with somatostatin analog in the therapy of functional endocrine tumors. 246 Sep 58

The clinical, microscopic, immunohistochemical and ultrastructural features of 7 gastrinomas and 1 combined carcinoma-carcinoid tumor were evaluated. The tumors were located in the pancreas or duodenal wall in 6 cases, and on extragastro-enteropancreatic sites in 2 (liver or peripancreatic lymph node). All patients had the Zollinger-Ellison syndrome, 3 of them with additional bleeding and 1 with diarrhea. One patient with gastrinoma had additional tumors characteristic of the MEN-I syndrome. Immunohistochemistry showed gastrin and neuron-specific enolase-positivity in all of the tumors. Somatostatin was found in 4 cases, and single cell glucagon, pancreatic polypeptide. S-100 protein, keratin as well as carcino-embryonic antigen positivity in another few. Additional hormone production did not appear to be connected with biological behaviour of the tumors or with the clinical symptoms.
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PMID:Studies into gastrinomas and combined carcinomatous carcinoid tumors. Optical light- and electron microscopy and immunohistochemistry. 248 34

The characterization of the tumors and their metastasis in patients with the Zollinger-Ellison syndrome is currently based on the immunohistochemical identification of gastrin cells. However, sometimes tumoral cells fail to react with common C-terminal gastrin antibodies. In order to clarify this failure, we carried out morphologic, morphometric and immunocytochemical analyses performed on light and electron microscope levels of 6 pancreatic and 1 metastatic gastrinomas, using antibodies raised against various sequences of human progastrin. On the basis, in light microscopy, of qualitative analysis of immunostaining within cells and of immunostained cell numbers, gastrin 34 residue seemed to be the prominent form in 2 of the tumor tissues, G-17 in 1 tumor which was not responsive with C terminus progastrin and N terminus G-34 antisera, and progastrin in the metastatic tissue that did not contain typical gastrin (G-like) cells. Two tumors failed to react with all antisera used. At the electron microscope level, immunogold staining revealed that progastrin was present only in the progranules and gastrin 34 in both progranules and intermediate granules. Quantitative studies performed on 3 tumors showed that, within a given tumoral cell, about 25 percent of progranules contained progastrin while 75 percent contained gastrin 34. We concluded that different forms of gastrin can be immunodetected in a gastrinoma tissue, depending on the regions, and that the distribution of progastrin fragments is variable from tumor to tumor. So, specific antibodies to different fragments of progastrin may help to the characterization of gastrinomas.
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PMID:Immunohistochemical characterization of gastrinomas with antibodies specific to different fragments of progastrin. 248 14

There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.
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PMID:Gastrin processing in primary culture of gastrinoma cells. 248 43

Human endocrine tumours were studied in in vitro systems (cell suspensions and tissue cultures) and in in vivo systems (tumour transplants to the anterior eye-chamber of immunosuppressed rats). In the experimental systems the tumour cells were demonstrated to synthesize and secrete the same hormonal products as in the patient. Intraocular transplants of a gastrinoma secreted gastrin-17 into the chamber fluid. This molecule, normally not secreted in the rat, was also detected in the peripheral plasma of tumour-bearing rats. Intraocular transplants of midgut carcinoid tumours released serotonin (5-HT) at adrenoceptor stimulation, of a similar type as demonstrated in acute tumour cell suspensions. However, in tissue cultures genuine beta-adrenoceptors seemed to be modified, since pretreatment with beta-adrenoceptor antagonists or calcium deprivation did not prevent stimulated 5-HT release. Tachykinins were not liberated by adrenoceptor stimulation. In certain cultures of midgut carcinoid tumour cells, two different phenotypes developed: small rounded endocrine tumour cells with positive immunoreactions against 5-HT and tachykinins (TK), and large elongated neuron-like cells, which gradually lost 5-HT immunoreactivity, while TK immunoreactivity remained unchanged. These cultured tumour cells may produce an endogenous factor inducing transformation into a neuron-like phenotype. One candidate factor is nerve growth factor (NGF), since NGF-like immunoreactivity was demonstrated in cells of the endocrine phenotype.
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PMID:Expression of gastrointestinal endocrine tumours in culture systems. 251 Jul 85

A total of 143 patients with peptic ulceration of the duodenum, stomach or oesophagus, who did not respond to 3 or more months high-dose treatment with ranitidine (450 mg or more daily), were admitted to oral treatment with omeprazole, 40 mg/day. In 94.4% of the patients, ulcers healed within 2-6 weeks. After healing of their ulcers, 122 patients were admitted to long-term maintenance treatment with omeprazole, 40 mg/day; 91 patients have been on the drug for 1-5.5 years. During maintenance therapy with omeprazole, 40 mg/day, no relapses (verified by endoscopy) have yet occurred and no drug related adverse effects have been observed. There were no significant changes in routine laboratory tests in any patients, including 27 with concomitant liver cirrhosis. Serum gastrin levels were already elevated approximately 2-fold during the initial high-dose ranitidine treatment and rose a further 2-fold at 2-3 months of omeprazole treatment. Thereafter, no further increase of serum gastrin was observed even after 5.5 years of continuous observation. Volume density of G and D cells in the antral mucosa did not change significantly. The volume density of argyrophilic cells in the oxyntic mucosa was 0.73 +/- 0.1% before the start of omeprazole treatment and 0.85 +/- 0.09% after 17-24 months of continuous treatment with omeprazole (ns). In antrectomized patients the volume density was lower (0.23 +/- 0.04%). No clusters of argyrophilic cells were observed in any of the groups. In a control group of patients with gastrinoma the volume density of these cells was higher (1.3 +/- 0.23%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Omeprazole in the long-term management of patients with acid-related diseases resistant to ranitidine. 251 41

Two patients with Zollinger-Ellison Syndrome were diagnosed and treated in PUMC Hospital, the primary tumors were found in the stomach. On sectioning of the gastrectomized specimens, 85 tumors ranging from 0.1 to 1.0 cm in diameter were disclosed in Case 1, and a large ulcero-infiltrative carcinoma-like tumor in Case 2. Both tumors had already metastasized to regional lymph nodes and/or liver. Tumor cells in both cases exhibited gastrin, NSE, GH and hCG alpha immunoreactivity immunocytochemically, and abundant neurosecretory granules of 100-250 nm in diameter under electron microscope. The clinicopathological, immunocytochemical and ultrastructural findings of tumors from these two cases met the criteria of primary malignant gastrinoma of the stomach.
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PMID:Gastric gastrinoma. 251 58

In summary, although similar imaging techniques are used for the localization of insulin and gastrin secreting islet cell tumors, the success rates are very different. Fortunately, the best results are obtained in the tumor for which effective medical treatment is less available, namely insulinomas, which can be found and successfully resected in over 90 per cent of patients. Both portal venous sampling and experienced intraoperative ultrasound are critical for successful surgery of small insulin-secreting tumors. Facilities without these resources should not explore patients when the conventional imaging studies are negative. Gastrinomas, on the other hand, will elude detection by even the most experienced surgeons in over 20 per cent of patients with sporadic Zollinger-Ellison syndrome in spite of positive portal venous sampling and intra-arterial secretin studies. The very small size of these tumors and their occurrence in more difficult to explore extrapancreatic sites provides the basis for this difference. However, patients with negative imaging studies and negative surgical explorations have an excellent prognosis on long-term follow-up when gastric acid hypersecretion is controlled. An annual computed tomographic scan is recommended since the appearance of a tumor would mandate surgical resection because of the significant incidence of malignancy in larger tumors. However, progression to imageable tumors has been unusual in our experience with this group of patients. There remains a small group of patients with highly malignant, rapidly metastasizing, gastrin-secreting islet cell carcinomas for whom localization is simple but of little relevance. However, locally invasive gastrinomas may often be resectable and provide prolonged remission and even cure. Aggressive surgery, supported by detailed cross-sectional and angiographic localization, has a role in this small group of patients.
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PMID:Localization of islet cell tumors. 255 33

In patients with Zollinger-Ellison syndrome, serum gastrin level is increased by secretin and is decreased by somatostatin. To elucidate the cellular mechanism for these actions, we investigated the direct effects of secretin and somatostatin on dispersed gastrinoma cells from a patient with Zollinger-Ellison syndrome. In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin. In the presence of guanosine 5'-triphosphate, furthermore, secretin enhanced adenylate cyclase activation in the membranes from these cells, and this activation was reduced by somatostatin, whereas neither secretin nor somatostatin affected inositol phospholipid turnover. On the other hand, removal of guanosine 5'-triphosphate from incubation medium abolished both the stimulatory effect of secretin and the inhibitory effect of somatostatin on adenylate cyclase activation. Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase. Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins.
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PMID:Mechanism for increase of gastrin release by secretin in Zollinger-Ellison syndrome. 261 6

Multiple endocrine neoplastic diseases are genetically determined conditions with particular organ patterns for endocrine tumors. In Type I or Wermer's syndrome the endocrine pancreas, anterior pituitary and parathyroids are involved, insulinoma being the most frequent pancreatic tumor. To facilitate diagnosis, a prolonged oral glucose tolerance test, a fasting test and determination of the glucose-insulin ratio are recommended. Localisation is sought by computer tomography and angiography. A gastrinoma is excluded on the basis of normal gastrin levels in serum and by means of the secretin-provocation-test. Pituitary tumors can be classified more closely with prolactin levels and releasing-hormone tests (LH-RH and TRH). Prolactinoma is the most frequent pituitary tumor and amenable to bromocryptin treatment. If Wermer's syndrome is suspected, primary hyperparathyroidism has to be excluded on the basis of calcium and parathormone levels. Chief cell hyperplasia or multiple adenomas are frequent. Surgical resection is necessary.
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PMID:[Type I multiple endocrine neoplasia--Wermer syndrome]. 257 44


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