Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.
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PMID:Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas. 242 19

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.
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PMID:Evaluation of NH2-terminus gastrins in gastrinoma syndrome. 287 76

The basal concentrations of sulfated and non-sulfated gastrins in serum were measured radioimmunochemically in healthy subjects and in normo- and hyper-gastrinemic diseases. The degree of sulfation in patients with duodenal and gastric ulcer, chronic pancreatitis, gallstone disease, and chronic renal failure were similar to that of healthy controls, in whom 37.7 +/- 1.9% (mean +/- SEM) of serum gastrins were sulfated. In eight patients with the Zollinger-Ellison syndrome 57 +/- 5.4% of the gastrins were sulfated (p less than 0.005, compared with controls). In patients with pernicious anemia (no. = 20) only 24.4 +/- 2.0% of the gastrins were sulfated (p less than 0.005, compared with controls). An inverse correlation (r = -0.63, p less than 0.01) was found between the degree of sulfation and the total gastrin concentration in pernicious anemia but not in gastrinoma patients. The results indicate that diseases with increased synthesis of gastrin are accompanied by an abnormal degree of sulfation.
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PMID:Variations in the sulfation of circulating gastrins in gastrointestinal diseases. 666 33

We determined the relative concentrations of gastrin molecular species in serum samples from 21 patients with Zollinger-Ellison syndrome with localized gastrinoma (n = 11) or gastrinoma with hepatic metastases (n = 10). Gastrin molecular species were separated by gel-filtration chromatography and quantitated by radioimmunoassay with a gastrin antiserum produced in our laboratory. The percentage gastrin-17 of the total gastrin in the two groups differed significantly (nonparametric Wilcoxon rank test; p less than 0.01). Patients with the Zollinger-Ellison syndrome with apparently localized gastrinoma had a lower percentage of G- 17 (7.6%, SEM 1.6%) than did patients with gastrinoma with hepatic metastases (31.1%, SEM 6.1%). This procedure may be useful in the early classification of tumors in patients with Zollinger-Ellison syndrome.
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PMID:Serum gastrins in Zollinger-Ellison syndrome: identification of localized disease. 737 8

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.
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PMID:Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. 832 58