L.-I. Larsson

PANCREATIC SOMATOSTATINOMA: Clinical Features and Physiological Implications

The first case of a tumour producing somatostatin-like immunoreactivity and bioactivity is presented. The pancreatic tumour was composed of cells indistinguishable from islet D cells. Radioimmunoassay of blood-samples obtained by tumour-vein catheterisation revealed very high levels of somatostatin immunoreactivity. On gel chromatography tumour extracts were found to contain at least 4 different immunoreactive components, one of which eluted in the position of synthetic somatostatin. Extracts from the tumour were potent in inhibiting insulin and glucagon secretion from isolated perfused porcine pancreas. Clinical abnormalities included hypochlorhydria, steatorrhoea, and diabetic glucose tolerance. Conceivably some of these abnormalities may be related to somatostatin hypersecretion from the pancreatic tumour.

Occurrence of nerves containing vasoactive intestinal polypeptide immunoreactivity in the male genital tract

Abstract Immunocytochemistry and radioimmunochemistry demonstrates the occurrence of numerous nerves containing the vasoactive intestinal polypeptide (VIP) in the male genital tract. The nerves occur in association with arteries and smooth musculature of the organs. Available evidence suggests VIP to be a new neurotransmittor possibly involved in the regulation of blood flow and muscle contractility of the male genital organs.

Innervation of the pancreas by vasoactive intestinal polypeptide (VIP) immunoreactive nerves.

Abstract The vasoactive intestinal polypeptide (VIP) has been shown to exert effects on endocrine and exocrine pancreatic secretion. Immunocytochemistry reveals that VIP immunoreactive nerves occur in the porcine, canine, feline and avian pancreas. In the pancreas of pig and cat VIP nerves are abundant around non-immunoreactive nerve cell bodies of the intrapancreatic ganglia but scarce in the islets and in the exocrine parenchyma. In the dog pancreas, however, the intrapancreatic ganglia contain strongly immunoreactive VIP nerve cell bodies which give off axons that seem to heavily innervate vessels as well as endocrine and exocrine cells. We suggest that in the pig and cat the pancreatic VIP nerves mainly affect the activity of a second type of intrapancreatic neuron, whose transmitter is unknown, whereas in the dog pancreas VIP nerves directly contact their putative effector structures.

Potent inhibitory effects of transplantable rat glucagonomas and insulinomas on the respective endogenous islet cells are associated with pancreatic apoptosis.

Effects of transplantable rat insulinomas (IN) and glucagonomas (GLU) on the endogenous pancreas were analyzed using morphometry, immunocytochemistry, in situ hybridization, and staining for apoptotic cells. Hyperinsulinemia (IN-rats) and hyper-GLP-1/glucagonemia (GLU-rats) were both associated with marked islet atrophy (67 and 76% of control average planimetrical islet area, respectively). Selective islet B cell inhibition of proinsulin (I and II) genes as well as of expression of the insulin gene transcription factor, IPF1/STF1, was found in IN-rats. Moreover, these islets were characterized by significant B cells apoptosis in the absence of infiltrating lymphocytes. In GLU-rats selective islet A cell inhibition was observed at the level of glucagon mRNA. These islets contained small, highly condensed but clearly active B cells with prominent IPF1/STF1-positive nuclei, surrounded by densely packed glucagon-negative cells with reduced cytoplasm. Furthermore, an active apoptotic process was found exclusively in the exocrine pancreas of GLU-rats. Thus, in IN-rats, islet B cell mass reduction is distinguished by non-immune-mediated programmed cell death, while GLU-rats exhibit A cell mass reduction by cytoplasmic retraction and selective exocrine apoptosis.

Radioimmunochemical characterization of acthlike peptides in the antropyloric mucosa

Abstract Extracts of feline and human antropyloric mucosa contain two ACTH immunoreactive components. The main molecular component is radioimmunochemically and gel chromatographically indistinguishable from pituitary ACTH (1–39). Upon chromatography at two different pH, the main component and ACTH (1–39) displays identical changes in elution behaviour. In addition, antropyloric extracts contain a minor ACTH immunoreactive component, eluting in the void volume on Sephadex G-50 columns. The nature of this component is still undecided, but circumstantial evidence suggest that it may represent a biosynthetic precursor to the main ACTH-like component.

Radioimmunocytochemistry-a novel immunocytochemical principle.

Currently available immunocytochemical techniques rely on the detection of the antibody by means of direct labeling or indirect immunologic procedures. To increase immunocyto-chemical specificity a new radioimmunocytochemical method has been developed. In the radioimmunocytochemical method radiolabeled antigen is incubated with surplus amount of antibody. In this way only one combining site of the antibody will bind the labeled antigen, leaving the other site free to react with tissue-bound antigen. The site of reaction with tissue antigen is revealed by autoradiography. The radioimmunocytochemical method is specific and sensitive and can be combined with conventional staining methods or with immunoperoxidase techniques. It may also be useful for ultrastructural and quantitative immunocytochemistry.