1/15. Cure of acromegaly by operative removal of an islet cell tumor of the pancreas.We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH)-like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/15. High plasma pancreastatinlike immunoreactivity in a patient with malignant insulinoma.High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin a corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/15. A case of multiple endocrine neoplasia (men) type 1; the immunohistochemical and ultrastructural studies of its tumors and the analysis of hormones in tumor extracts.We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/15. Malignant somatostatinoma presenting with diabetic ketoacidosis.High circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). fasting insulin and c-peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non-small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohistochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin-like immunoreactivity, and calcitonin with focal immunoreactivity for SRIF, serotonin, neuron-specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF-like immunoreactivity (SRIF-LI): predominantly SRIF-28 and intermediates in tumour extract, and SRIF-14 and an intermediate between SRIF-28 and SRIF-14 in plasma, DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/15. Watery diarrhea syndrome caused by multihormonal malignant pancreatic islet cell tumor secreting somatostatin, vasoactive intestinal peptide, serotonin, and prostaglandin E--a clinicopathological, biochemical, immunohistochemical, and ultrastructural study.The pathophysiological, biochemical, histological, ultrastructural, and immunohistochemical characters of a case of malignant pancreatic islet cell tumor with watery diarrhea syndrome were carefully investigated. Four hormones or mediators--somatostatin (SST), vasoactive intestinal peptide (VIP), serotonin, and prostaglandin E--were markedly elevated in the circulation. The diagnosis was further confirmed by exploratory laparotomy and autopsy. The contents of SST and VIP in tumor tissues were very high. Gel chromatography of tumor extract revealed single peaks for both SST and VIP. Immunohistochemical studies of tumor tissues showed numerous immunoreactive cells to anti-SST, moderate amount of VIP-positive cells, and a few hCG-, insulin-, and glucagon-positive cells. In conclusion, this is an unusual case of Verner-Morrison syndrome in which three kinds of bioactive hormones or mediators were simultaneously secreted; peptides, amine, and prostaglandin.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/15. Somatostatin-secreting islet cell tumor (somatostatinoma): suppression of growth hormone (GH) release induced by GH-releasing hormone.A patient with a somatostatin (SRIH)-secreting islet cell tumor, whose only symptoms were dyspepsia and anemia, is described. The diagnosis of somatostatinoma was based on high plasma SRIH concentrations and immunocytochemical findings. The pancreatic exocrine response to secretin was decreased, whereas the insulin and/or glucagon responses to glucose and arginine were normal. Although the basal plasma GH concentration was normal, the plasma GH response to GHRH was subnormal. Gel permeation chromatography studies indicated that SRIH-14 was the predominant form of SRIH in plasma as well as in tumor tissue.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/15. Secretory response and immunochemical heterogeneity of glucagon in plasma and tumor extracts of a patient with glucagonoma.The secretory response and immunoreactive heterogeneity of glucagon was investigated in a patient with glucagonoma syndrome. After glucose administration, abnormal insulin release accompanied by glucose intolerance were observed, whereas the high glucagon circulating levels were only partially blocked after glucose or somatostatin infusion. Chromatographic fractionation of plasma samples, before and after arginine administration showed that most of the immunoreactivity eluted as true glucagon. Furthermore, when aliquots of the tumor extracts were fractionated by column chromatography or by polyacrylamide gel electrophoresis, most of the immunoreactivity eluted in the 3,500 molecular weight peak. In contrast with previous reports, our results indicate that neoplasia A cells can also manufacture and release into the bloodstream great amounts of genuine glucagon rather than larger glucagon immunoreactive forms. In spite of such findings, in this patient neither diabetes nor hyperglycemia were present.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/15. Aberrant insulinoma in the duodenum.A rare case of aberrant insulinoma in the duodenum is described. Hyperinsulinemia with typical hypoglycemic symptoms was induced by prolonged fasting. Selective angiography demonstrated a tumor supplied from the first branch of the jejunal artery, and duodenoscopy revealed a submucosal tumor at the third portion of the duodenum. An increase in venous plasma immunoreactive insulin concentration was evident in the vein draining from the tumor, by sampling through percutaneous transhepatic catheterization. hypoglycemia was ameliorated after the removal of the submucosal tumor of the duodenum. Histologic and immunocytochemical characterization of the tumor showed an insulinoma, predominantly composed of cells with typical B-cell-like granules. The acid extract of the tumor contained 1.2 U/g of insulin, and this insulin, analyzed by reverse-phase high-pressure liquid chromatography, revealed that it had the same amino acid structure as that of human insulin.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/15. Cushing's syndrome due to ectopic proopiomelanocortin gene expression by islet cell carcinoma of the pancreas.Expression of proopiomelanocortin (POMC) was studied in a male patient with Cushing's syndrome and ectopic production of ACTH by a pancreatic carcinoma. plasma ACTH levels (greater than 200 pg/ml) were elevated, and elevated serum cortisol and urinary free cortisol were partially suppressed to 25% of basal levels by high-dose dexamethasone. Petrosal and jugular vein sampling did not yield a gradient of ACTH. Immunohistochemical staining of tumor tissue removed at pancreatectomy was positive for ACTH and beta endorphin, and negative for corticotropin-releasing factor (CRF). Tumor cells cultured in vitro secreted ACTH and beta-endorphin, which comigrated with their respective radiolabeled standards on gel chromatography. hydrocortisone suppressed in vitro ACTH secretion and CRF (100 nM) stimulated ACTH by 50% during 72 hours of incubation. Agarose gel electrophoresis of poly-(A) mRNA extracts of tumor tissue followed by hybridization with 32P-cDNA for POMC revealed 2 distinct rna species. The major rna species (about 1.0 kb) was smaller than authentic pituitary POMC mRNA (about 1.1 kb); a larger precursor band also was visualized, suggesting either processing or degradation of tumor-POMC mRNA. Cytoplasmic dot blot hybridization of tumor mRNA with POMC cDNA yielded a positive signal with increasing amounts of rna blotted. immunohistochemistry and radioimmunoassay (RIA) of ACTH, in vitro regulation of ACTH secretion, and expression of POMC mRNA species by this tumor document expression of the human POMC gene by an islet carcinoma associated with Cushing's syndrome.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/15. The glucagonoma syndrome: stimulus-induced plasma responses of circulating glucagon components IRG9000 and IRG3500.plasma responses of the major immunoreactive glucagon (IRG) components have been investigated in a case of glucagonoma syndrome. fasting plasma IRG was 4155 pg/ml. Gel chromatography of plasma revealed that 66% of immunoreactivity was present as IRG9000, while IRG3500 accounted for an additional 26%. The appearance in peripheral plasma of these two glucagon fractions was examined after administration of a number of compounds. IRG levels were clearly elevated after arginine and tolbutamide. Both calcium and calcitonin induced a biphasic rise of IRG, the increase being slower after calcium administration. Somatostatin suppressed plasma IRG levels. All tests induced changes in both IRG3500 and IRG9000. In general, relative changes were more pronounced in IRG3500 than in IRG9000, while absolute changes were greater in IRG9000. The shape of the response curves of IRG3500 and IRG9000 was quite similar after arginine, calcium and somatostatin. After tolbutamide the IRG9000 response was delayed as compared to the IRG3500 component. During the latter part of the calcitonin infusion, IRG9000 remained elevated while IRG3500 was back at its starting level.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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