Biomedical subjects
Publications and source records attributed to F Sundler.
The ACTH cells of human foetal pituitary displayed intense formaldehyde-ozone-induced fluorescence characteristic of peptides or proteins with NH2-terminal tryptophan. Fourteen pituitary tumours were examined histochemically. Of these, two displayed formaldehyde-ozone-induced fluorescence. These two tumours were the only ones to exhibit ACTH immunoreactivity.
Numerous epithelial cells in the oxyntic gland area of the stomach of cat and dog appear to store pancreatic-type glucagon, as evidenced by immunohistochemistry and--in the case of the dog--also by radioimmunoanalysis. No glucagon immunoreactive cells are found in the antropyloric mucosa. Disseminated cells in the intestinal mucosa store gut-type glucagon. In all species studied, these cells predominate in ileum and colon.
Fluorescamine is a useful fluorescence microscopic reagent for the demonstration of certain peptide hormone-secreting cells in formaldehyde-fixed tissues. Among the cells demonstrated are the pituitary GH cells, the gastrin cells, the insulin cells and the thyroid C cells. In the latter cell system degranulation brings about a marked decrease in the intensity of the fluorescamine-induced fluorescence suggesting that the fluorogenic component is associated with the secretory granules. In models neither of the hormones tested--GH, gastrin, insulin--gave fluorescamine-induced fluorescence after pretreatment with formaldehyde. It is suggested that the fluorescamine-induced fluorescence of the endocrine cells demonstrates granular components distinct from the hormones.
In several mammals the antral gastrin cells display characteristic formaldehyde-ozone-induced fluorescence (375/500-520 nm). Such fluorescence is also given by gastrinoma cells. Gastrin granules, isolated from gastrinomas and identified by immunofluorescence and electron microscopy, were found to show intense formaldehyde-ozone-induced fluorescence.
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HPP is the human counterpart of APP--a polypeptide that has been isolated from avian pancreas and shown to exert pronounced biological effects. The availability of anti-HPP serum enabled us to use immunohistochemical procedures for the localization of HPP in human pancreas. A small population of pancreatic islet cells showed strong immunofluorescence after staining with anti-HPP serum. The HPP cells were mainly localized at the periphery of the islets. Sometimes they were also seen scattered in the exocrine parenchyma as well as within the epithelium of small to medium-sized ducts. While rare in the pancreas of adult man, HPP cells were abundant in certain parts of the pancreas of foetuses (18-20 weeks gestational age). Their staining properties showed them to be distinct from the A, Band D cells of the pancreatic islets.
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.
Substance P immunoreactivity has been demonstrated in the mouse gut in two distinctly different locations; in the myenteric plexus of the proximal colon as well as in endocrine-like cells of the duodenal and colonic mucosa.
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Fluorescence microscopy has demonstrated formaldehyde-ozone-induced fluorescence in the pars intermedia cells (melanocyte-stimulating hormone cells) and in certain cells of the pars distalis of the mammalian pituitary. From histochemical and chemical evidence the fluorescence is believed to reflect the presence of peptides with NH2-terminal tryptophan. In the pars distalis of hamster, cat and pig pituitary, the cells that exhibit formaldehyde-ozone-induced fluorescence have now been identified as adrenocorticotrophic hormone (ACTH) cells by immunohistochemistry. Granules from pig pituitaries were purified by passage through a succession of Millipore filters followed by centrifugation on a continuous sucrose gradient. Two granular fractions were identified by electron microscopy and found to contain high concentrations of peptides with NH2-terminal tryptophan as well as high ACTH bioactivity. These fractions, when pelleted and analyzed histochemically, displayed formaldehyde-ozone-induced fluorescence and ACTH-like immunoreactivity.
Treatment with formaldehyde gas and HCl vapor, simultaneously or in sequence, induces fluorescence with indoles, including tryptophan residues of peptides, as is evident from studies on protein droplet models. Among cells that display intense formaldehyde-HCl-induced fluorescence are pancreatic exocrine cells, gastric chief cells, Paneth cells and enterochromaffin cells. Peptide hormone-producing cells that can be visualized by the formaldehyde-HCl treatment include gastrin cells and glucagon cells. The simultaneous procedure has proved superior to the sequential procedure. Simultaneous formaldehyde-HCl treatment appears to be a useful method for the demonstration of tryptophan residues of peptides and proteins. It seems more sensitive than previously described indole methods.
Fluorescence histochemistry was used to study the sympathetic innervation of the thyroids from adult individuals of six different species; mouse, rat, hamster, dog, sheep, and pig. In addition, thyroids from very young rats and from very old mice were examined. Generally, thyroidal sympathetic, adrenergic nerve terminals were found not only as a network around vessels, but also as single terminals between, and sometimes around, follicles. Interfollicular terminals were numerous in thethyroids of adult mice, sheep and hamsters, but they were few in the thyroids of adult rats and dogs, and even fewer in the porcine thyroid. In contrast to the findings in thyroids from adult mice and rats, several interfollicular terminals were found in thyroids from very young rats while very few such terminals were detected in the thyroids from very old mice. The observations suggest that there is a pronounced interspecies variation in the number of thyroidal interfollicular sympathetic nerve terminals and that, at least in the rat and the mouse, there is also a variation with age. Since, in mice, sympathetic activation appears to induce thyroid hormone secretion by a direct action of norepinephrine released from intrathyroidal sympathetic fibers, the recorded variations are presumed to have functional importance.
The influence on thyroid hormone secretion of the nonselective beta-adrenergic stimulant isoproterenol (IPNE), of a selective beta1-adrenergic stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol (ITP), and of a selective beta2-adrenergic stimulant, terbutaline, was investigated in mice. A combination of light microscopy (colloid droplet formation) and bioassay (blood radioiodine--BRI--measurements) was used. IPNE and terbutaline induced formation of colloid droplets and increased BRI levels, whereas ITP was ineffective. The responses to IPNE and terbutaline were abolished or reduced by pretreatment with L-propranolol, but were not inhibited for pretreatment with D-propranolol or phentolamine. The results indicate that secretion of thyroid hormone can be induced through the mediation of beta2-adrenergic receptors.
In the guinea-pig pancreas, 5-hydroxy-tryptamine (5-HT) occurs in the B-cells as well as in enterochromaffin cells scattered in the exocrine parenchyma. In the present study we examined the effects on the pancreatic 5-HT and insulin content of drugs known to affect the B-cells. For this purpose a radioimmunoassay of guinea-pig insulin was developed. Streptozotocin reduced the number of detectable B-cells and partially degranulated those that remained. It also lowered the insulin content of the pancreas and the 5-HT content of the B-cells but did not affect the 5-HT content of the enterochromaffin cells. Reserpine lowered the 5-HT content of both B-cells and enterochromaffin cells. The number and ultrastructure of the B-cells and the pancreatic insulin content was not affected. Streptozotocin + reserpine seemed to have additive effects of B-cell 5-HT. The results with these 2 drugs indicate that roughly 50% of pancreatic 5-HT is contained in the B-cells. Diazoxide markedly increased the pancreatic insulin content without affecting pancreatic 5-HT. Despite the fact that 5-HT and insulin are stored together in the cytoplasmic granules of the B-cells, 5-HT was differentially depleted from this store by reserpine. A marked disproportionality between 5-HT and insulin content was also induced by diazoxide.
The possible significance of thyroid mast cells in the regulation of thyroid blood flow and capillary permeability was investigated in rats whose TSH secretion had been eliminated by exogenous T4. Mast cells were identified by their abundance of metachromatic granules, and their content of histamine and 5-hydroxytryptamine (5-HT) was examined by fluorescence histochemistry. Thyroid histamine levels were determined by fluorometry. The tissue uptake of 86Rb was used as an indicator of blood flow and permeability. Numerous histamine- and 5-HT-containing mast cells were found within the thyroid and in connective tissue adjacent to the thyroid, whereas juxtathyroidal muscle tissue was virtually devoid of mast cells. Administration of compound 48/80 evoked a prompt depletion of 5-HT, histamine and metachromatic granules from thyroid mast cells, and a concomitant increase in the thyroidal uptake of 86Rb. The 86Rb uptake by juxtathyroidal muscle tissue was unaffected. Exogenous 5-HT and histamine both induced prompt increments in thyroidal 86Rb uptake, and 5-HT also stimulated 86Rb uptake in juxtathyroidal muscle tissue. TSH, previously shown to induce a gradual amine release from mast cells within, but not outside, the thyroid, evoked a gradual increase in thyroidal, but not in muscular, uptake of 86Rb. The findings support the concept that, in the rat, histamine and/or 5-HT, released from intrathyroidal mast cells by TSH, stimulate thyroid blood flow and/or permeability.
Immunoreactive gastrin cells were demonstrated in the human antral and duodenal mucosa. No gastrin immunoreactivity was seen in pancreatic islets. Formaldehyde- or Bouin-fixed material was used throughout for immunohistochemistry. Antral and duodenal gastrin cells, as well as pancreatic A2-cells, displayed strong formaldehyde- ozone- and formaldehyde-HCl-induced fluorescence, whereas the pancreatic A1-cells (claimed to store gastrin) were nonfluorescent. In the fetus, gastrin cells appeared first in the duodenal mucosa (earliest stage examined, 11 weeks) and much later in the antrum. The fluorescence histochemical properties of the fetal gastrin cells were not different from the adult.
Twenty-four endocrine pancreatic tumors were examined immunohistochemically for insulin, glucagon, gastrin and ACTH. In seven of these tumors, more than one peptide-hormone-containing cell type was observed. These seven tumors were also examined with conventional staining methods for the presence of A1, A2, and B cells. The results showed that these staining methods do not always distinguish between the different hormone-producing cell types of endocrine pancreatic tumors. In spite of the fact that several types of hormone-secreting cells were found in the tumors, the case histories described symptoms characteristic of hypersecretion of only one of the hormones. The hormone of the predominating cell type could not always explain the clinical symptoms. Our results indicate the endocrine pancreatic tumors often are multihormonal. Therefore, it would seem advisable to screen serum from all insuloma patients for a variety of peptide hormones.