Tribute to professor Giovanni Prenna.
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Biomedical subjects
Publications and source records attributed to E Solcia.
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Evidence was obtained by the use of alternate semithin-thin serial secretions for light and electron microsocpy that the I cell is the source of CCK PZ. The antibodies used were raised to a synthetic fragment of the mid part (9-20) of the (1-33) CCK-PZ molecule, and were thus free from any contamination with cross-reacting subpopulations of antibodies that might bind to gastrin.
The two anthracycline antitumor antibiotics, Adriamycin and daunomycin (DM), induced a high incidence of mammary tumors, both fibroadenomas and adenocarcinomas, in female rats that received a single i.v. dose, thus confirming previous results. The incidence of DM-induced adenocarcinomas increased with the dose of the drug, whereas the incidence of Adriamycin-induced adenocarcinomas showed a plateau at 5 mg/kg and above. Adriamycin- and DM-induced fibroadenomas showed a peak at lower doses (about 5 to 6 mg/kg). With the highest DM dose (12.5 mg/kg) used, there was a slight prevalence of adenocarcinomas over fibroadenomas.
In the dog ileum, neurotensin cells stained with immunofluorescence or immunoperoxidase proved distinct from argentaffin (EC) cells, glucagon immunoreactive (GLI) cells and pancreatic peptide immunoreactive (PP) cells. Neurotensin cells showed various degrees of reactivity with Grimelius' silver. With electron microscopy, besides EC cells, large granule cells with a thin peripheral rim of Grimelius-reactivity (L cells) and large granule cells with variable Grimelius-reactivity of the core (N cells) were found. On distributive grounds, L cells were identified with GLI cells and N cells were interpreted as neurotensin cells.
Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by "active" or "Stem cell" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.
Using antibodies against pure porcine VIP in immunoperoxidase and immunofluorescence tests, VIP-immunoreactive cells have been detected in the pancreas-especially in the islets-and gastrointestinal mucosa of the dog, guinea-pig and man. VIP immunoreactive cells were widely distributed in these tissues, never being numerous at any site. Some parallelism has been noted between such cells and ultrastructurally identified D1 cells fo the pancreas and gastrointestinal mucosa. The presence of VIP cells in normal pancreas may help explain the occurrence of pancreatic endocrine tumors producing VIP.
The bombesin group of hormonal peptides produced in the amphibian skin have powerful actions on the mammalian gastrointestinal tract. In man a bombesin-like material was found in an endocrine cell which is widely distributed in the gastrointestinal mucosa. This has tentatively been identified as belonging to the non-enterochromaffin cell groups. The large number of cells containing a bombesin-like peptide suggests that this substance may be important in human physiology.
Coordinated studies have been carried out on the glucagon immunoreactive cells of the mammalian gastrointestinal tract (man, dog, rat), using electron microscopy, silver staining and immunocytochemistry. Parallel ultrastructural and immunocytochemical studies have been made with the semithin-thin serial section technique. The results indicate that while the glucagon cells of the oxyntic portion of the stomach are virtually indistinguishable from those of the pancreatic islets (A cells) those of the intestine (EG cells) are completely different. Proper identification of glucagon immunoreactive cells requires the application of morphological and silver staining techniques, at the ultrastructural level.
In indirect immunofluorescence tests, antibodies against pure porcine cholecystokinin (CCK) have detected specific CCK cells in the duodenal and jejunal mucosa of the dog and man. The CCK cells were scattered in the epithelium of the crypts, although some were in the villi. No CCK cells were found in the stomach, pancreas, terminal ileum, or colon. Some pyloric G cells also showed some reactivity with CCK antiserum, but absorption of CCK antiserum with gastrin C terminal pentapeptide prevented the staining of pyloric cells and provided specific staining of intestinal CCK cells. Anti-human gastrin I serum stained some intestinal cells too. Most of such cells did not react when gastrin antiserum was absorbed with pure CCK (a treatment that did not prevent the staining of pyloric gastrin cells); they were interpreted as cross-reacting CCK cells rather than as intestinal gastrin cells.
Small intestinal mucosal samples from man, pig and dog, were subjected to sequential or correlative silver impregnation techniques, applied to immunocytochemical preparations and at the ultrastructural level. The cell reacting with anti-GIP sera was identified as the ultrastructurally classified K cell and we propose that the term GIP cell be used in place of the latter. This cell can thus be recognized by its strong reactivity with the Sevier-Munger staining procedure, provided that the equally strongly reacting EC cell is excluded by virtue of its argentaffinity with the Masson technique.
Material from eight peptide hormone-secreting tumours, extirpated from the pancreas or from the antrum-duodenum region, was examined. Four of the patients had the clinical manifestations of the Zollinger-Ellison syndrome, two showed the features of an insulin-secreting tumour and one had a glucagonoma. Gastrin-producing cells, identified by immunohistochemistry, were found in five of the tumours. These cells displayed a varying degree of formaldehyde-ozone-induced fluorescence. This agrees with previous observations on the gastrin cell of human antral and duodenal mucosa. From model experiments, formaldehyde-ozone-induced fluorescence is thought to reflect the presence of peptides having tryptophan in the NH2-terminal position. The nature of this peptide in gastrin-producing cells is unknown.
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