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Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 397 records · Page 22Linked to original sources
PubMed1983

Peptidergic innervation in Hirschsprung's disease.

An increasing amount of evidence concerning the existence of non-adrenergic, non-cholinergic autonomous nerves has been presented during the past decade. These nerves contain different peptides which may act as neurotransmitters. The pathophysiology in Hirschsprung's disease is not yet fully explained. To throw further light upon it, the distribution and occurrence of different peptide-containing (peptidergic) nerves was studied. A semiquantitative immuno-histochemical method was used to assess the distribution and occurrence of nerves containing encephalin, GRP (gastrin-releasing peptide), VIP (vasoactive intestinal peptide) or substance P in four patients operated by Duhamel's procedure. The results indicate a total absence of encephalin and GRP containing nerves in the aganglionic segment. Such nerves could, however, be found in the normally ganglionated part of colon. The nerves containing VIP and substance P were fewer in the aganglionic segment than in the rest of the colon. The result is related to what is hitherto known about the specific effects of the different peptides.

Colon↗
PubMed1983

Endocrine tumors of the duodenum. Clinical characteristics and hormone content.

Nineteen patients with primary duodenal carcinoid were analysed retrospectively, and eight of the tumors were immunocytochemically examined. One tumor contained somatostatin, two tumors gastrin, two tumors both these peptides, and one tumor contained serotonin. In two tumors no peptide or amine could be demonstrated. Eight patients had ulcer symptoms and nine had gallstone disease. Only four patients had metastatic spread in spite of long delay. Five-year survival was 75% in 12 operated patients. No patient died of the tumor per se. It is concluded that a simple excision seems justified when the tumor is smaller than 2 cm, while probably more extensive surgery is needed when the tumor is larger or when there is local spread. Modern techniques of histofluorescence and immunocytochemistry facilitating a more precise classification will probably result in a better understanding as to symptomatology, prognosis, and making possible better treatment in the heterogenous group of carcinoid tumors.

Adult↗
PubMed1983

Substance P fibres in the anterior segment of the rabbit eye.

Some laboratories have obtained diverging results regarding the presence of substance P fibres in the cornea possibly because different antibodies were used. This has been further investigated by comparing results with several antibodies on identically treated sections from the anterior segment of rabbit eyes. In the uvea all antisera gave identical results showing substance P fibres in the iris and ciliary processes. In the cornea, on the other hand, polyclonal rabbit or guinea-pig antibodies gave high background fluorescence and no immunofluorescence fibres were detected. In contrast, the background staining was low with the monoclonal antibody so that substance p immunoreactive fibres could be demonstrated subepithelially, intraepithelially and in the corneal stroma.

Animals↗
PubMed1983

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group.

Adolescent↗
PubMed1983

Gastric inhibitory peptide-like immunoreactivity in glucagon and glicentin cells: properties and origin. An immunocytochemical study using several antisera.

Although gastric inhibitory peptide (GIP) has never been detected outside the upper small intestine by immunochemical methods, GIP-like immunoreactivity has been demonstrated by immunocytochemistry in the glucagon/glicentin cells of pancreas, and gut. In the present study several GIP antisera (five polyclonal and one monoclonal) were tested on specimens from pancreas and intestines of several mammalian species, including man. Two of the polyclonal antisera and the monoclonal one stained cells in the upper small intestine only, while the other three also stained cells in the pancreas, ileum, and colon. Monoclonal anti-GIP did not stain GIP cells in man. The immunostaining produced could not be abolished by pretreatment of the antisera with glucagon or glicentin in excess, whereas small amounts of synthetic or natural porcine GIP prevented the immunostaining. Thus, three of the antisera are specific for GIP, while the other three recognize not only GIP but also GIP-like peptides. The results suggest that the glucagon/glicentin cells contain peptides distinct from GIP but sharing an immunodeterminant with GIP. The GIP-like immunoreactivity in the glucagon cells of the rat pancreas was not altered by infusion of GIP or by elimination of the bulk of endogenous GIP by resection of the upper small intestine, indicating that the GIP-like peptide is produced in the glucagon cells rather than accumulated from the circulation. The nature of this GIP-like peptide is unknown. Conceivably, it represents the cryptic portion of the glucagon precursor molecule. In some species a proportion of the GIP cells in the proximal small intestine displayed glicentin-like immunoreactivity as well, emphasizing the relationship between GIP cells on the one hand and glucagon/glicentin cells on the other.

Animals↗
PubMed1983

Neuropeptides in the thyroid gland: distribution of substance P and gastrin/cholecystokinin and their effects on the secretion of iodothyronine and calcitonin.

Previously, vasoactive intestinal polypeptide was localized to intrathyroidal nerve fibers. It stimulates iodothyronine secretion in mice. In the present study two populations of nerve fibers containing substance P and gastrin/cholecystokinin (CCK)-like immunoreactivity, respectively, were demonstrated in the thyroid gland of several mammals. The substance P fibers occurred around blood vessels and follicles, whereas the gastrin/CCK fibers occurred mainly around follicles. In the chicken thyroid and ultimobranchial glands only substance P-containing fibers could be demonstrated. Such fibers were particularly numerous in the ultimobranchial gland. CCK-4, CCK-8, and substance P did not increase thyronine secretion measured as release of radioiodine into the circulation of mice pretreated with Na125I and T4. The TSH-induced release of radioiodine was also unaffected. Calcitonin secretion in rats was stimulated by CCK-4, CCK-8, substance P, and vasoactive intestinal polypeptide.

Animals↗
PubMed1983

Neurohormonal peptides in endocrine tumors of the pancreas, stomach, and upper small intestine: I. An immunohistochemical study of 27 cases.

Preliminary observations have indicated the existence of characteristic spectra of gastroenteropancreatic (GEP) neurohormonal peptides in endocrine tumors arising in foregut, midgut, and hindgut derivatives. In order to further explore this feature of GEP endocrine neoplasms, islet cell tumors from 14 patients were studied, as were endocrine tumors of the stomach, duodenum, and upper jejunum from 6, 5, and 2 patients, respectively. All tumors were examined immunohistochemically with antisera raised against islet hormones [insulin, somatostatin, glucagon, pancreatic polypeptide (PP)], peptides of the gastrin family [gastrin, cholecystokinin (CCK)], peptides of the secretin family [secretin, vasoactive intestinal peptide (VIP)], and substance P, neurotensin, leu-enkephalin, beta-endorphin, motilin, calcitonin, and ACTH. In addition, an ultrastructural investigation was made. Whenever possible, the immunohistochemical observations were correlated with the clinical manifestations and with the results of radioimmunochemical determination of GEP neurohormones in the blood. The pattern of immunoreactive neurohormonal peptides and the clinical picture were those to be expected in endocrine tumors arising in foregut derivatives. Some principles are proposed for the classification of GEP endocrine tumors on the basis of their histopathologic growth pattern, their spectrum of neurohormonal peptides, and their clinical manifestations.

Adult↗
PubMed1983

Ontogeny of endocrine cells in porcine gut and pancreas. An immunocytochemical study.

A number of peptide hormones and hormone candidates were studied by immunocytochemistry with respect to their appearance and distribution in the developing porcine gastroenteropancreatic region. The hormones of the pancreatic islets were the first to appear. At 4 weeks' gestation (the earliest stage studied), glucagon, insulin, and somatostatin cells occurred in the dorsal pancreatic primordium, whereas pancreatic polypeptide cells occurred in the ventral primordium. At this stage, the pancreatic primordia were made up of strands of endocrine cells, and no ducts or acini were seen. Subsequently, the endocrine cells were separated by the growing exocrine parenchyma; at still later stages, they aggregated in small nests. Not until birth did they form mantle islets with insulin cells in the central core and the other endocrine cell types on the outside. Gastrin cells appeared in the stomach at the 4-wk stage; somatostatin cells appeared about 1 wk later. In the intestines, these two cell types appeared at the 6-wk stage. Cells displaying glucagon immunoreactivity were the first endocrine cells to appear in the intestine. They occurred in the upper small intestine at the 4-wk stage; they later disappeared from this location but appeared instead in the lower small intestine and colon where they remained. Secretin, cholecystokinin, motilin, gastric inhibitory peptide, and neurotensin cells all appeared at the 6-8-wk stage, and were restricted to the small intestine throughout development. Enkephalin immunoreactive cells appeared late during ontogeny (at the 13-15-wk stage) in both the gut and pancreas. Still later (15-17-wk stage), dense accumulations of endocrine cells (Segi's cap) were occasionally observed on the top of villi in the upper small intestine; these accumulations consisted mainly of somatostatin, cholecystokinin, and gastric inhibitory peptide cells. In view of the early appearance of many gastroenteropancreatic endocrine cell types in fetal life, a functional significance of gastroenteropancreatic hormones in the early development of gut and pancreas is likely.

Adrenocorticotropic Hormone↗
PubMed1983

Substance P-containing nerve fibers are numerous in human but not in feline intestinal mucosa.

The regional and topographic distribution of substance P-containing nerve fibers in the human and feline intestinal wall was studied by immunocytochemistry and radioimmunoassay. The concentration of substance P was measured in the different layers of the duodenum, jejunum, ileum, and colon. In both humans and cat, substance P fibers were fairly numerous, and the substance P concentration was comparatively high in the smooth muscle layer, including the myenteric ganglia. In humans, but not in cat, substance P fibers were numerous, and the substance P concentration was also high in the mucosa. Substance P-containing nerve cell bodies were observed in the myenteric ganglia of both species. In the submucous ganglia, such nerve cell bodies were seen in the human intestine only, suggesting that they represent the origin of the numerous mucosal substance P fibers in this species. Previous studies have revealed a relative paucity of substance P fibers in the intestinal mucosa of several mammals, such as mouse, rat, and pig. The cat can now be added to those having few mucosal substance P fibers, whereas humans seem to be notably rich in such fibers, suggesting that substance P may play a role in the regulation of mucosal functions in the human intestine.

Adult↗
PubMed1983

Endocrine cells in human intestine: an immunocytochemical study.

The regional and topographic distribution of endocrine cells in the human intestine was examined by immunohistochemistry. The frequency of endocrine cells was greatest in the small intestine with the rectum next in order. The duodenum and jejunum harbored a large number of different endocrine cell types; the spectrum of cell types gradually narrowed distally in the intestine. 5-Hydroxytryptamine-containing enterochromaffin cells were present in all regions of the intestine and comprised the single largest endocrine cell population. In addition, a minor proportion of these cells contained substance P. The second largest cell population consisted of the glicentin cells, which were notably numerous in the ileum and colon. The somatostatin cells also occurred throughout the digestive tract. Cells storing cholecystokinin, motilin, secretin, or gastric inhibitory polypeptide were more numerous in the proximal and middle small intestine than distally. Gastrin cells were few and occurred in the proximal duodenum only. Other cells in the small intestine reacted with antiserum directed against the common C-terminus of gastrin and cholecystokinin. The number of these cells greatly exceeded the sum of cells reactive to gastrin-specific or cholecystokinin-specific antisera. Cells displaying beta-endorphin, pro-gamma-melanocyte-stimulating hormone, or beta-lipotropin immunoreactivity, or a combination of these, were found in the small intestine. Cells storing neurotensin, glicentin, substance P, or pro-gamma-melanocyte-stimulating hormone increased in number distally in the small intestine. Enterochromaffin cells, glicentin cells, and somatostatin cells were the predominant endocrine cell types in the colon and rectum. The majority of the glicentin-immunoreactive cells also contained glucagon and pancreatic polypeptide-like immunoreactivity. Endocrine cells in the large intestine often possessed basal processes.

Adult↗
PubMed1983

Carcinoid tumors in the gastrointestinal tract--an analysis of 156 cases.

A series of 156 patients with gastrointestinal carcinoid tumors is presented. The tumors were grouped as foregut, midgut and hindgut carcinoids. The appendiceal tumors were grouped separately. Lack of specific symptoms resulted in only 26% correct presumptive diagnoses. This also reflected the patient's delay greater than 2 years in 10% and doctor's delay greater than 2 years in 29%. In the larger group (midgut), 41% were multiple primary tumors. Liver metastases were found in 46% and tumors bigger than 1 cm metastasized to the liver in 58%. The five-year survival of patients with liver metastases was 43% while the figure for those without metastases was 80%. In 47 patients with appendiceal carcinoids, 68% had tumors less than 1 cm. No metastases to the regional lymph nodes, viscera or skeleton were found. Thirty-three patients were traced and none had died of the tumor. Two foregut and 4 hindgut tumors were re-examined using immunocytochemistry. In one of the foregut tumors, cells containing serotonin were found while the other one contained gastrin cells. In 3 hindgut tumors PP-cells were seen and one of them also harbored glucagon/glicentin cells. In one hindgut tumor no peptides were found.

Adult↗
PubMed1983

Lack of vasoactive intestinal polypeptide nerves in esophageal achalasia.

Vasoactive intestinal polypeptide-containing nerves were examined in the lower esophagus of control and achalasia patients. The smooth muscle in patients with achalasia had conspicuously fewer vasoactive intestinal polypeptide-immunoreactive nerve fibers than specimens from control patients. Also the concentration of vasoactive intestinal polypeptide in the lower esophagus was much reduced in achalasia. In view of the potent smooth muscle relaxing effects of vasoactive intestinal polypeptide, it is suggested that the reduced number of vasoactive intestinal polypeptide fibers in the achalasic esophagus causes or at least contributes to the incomplete relaxation and the increased resting tone of the lower esophageal sphincter characteristic of this disease.

Adult↗
PubMed1982

Neurohormonal peptides in ovarian carcinoids: an immunohistochemical study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids.

Eighty-one primary ovarian carcinoids and intraovarian metastases from six mid-gut carcinoids were examined for the presence of tumor cells immunoreactive with antisera raised against various neurohormonal peptides, mostly of gastroenteropancreatic (GEP) origin. Twenty of the primary and two of the metastatic carcinoids contained such tumor cells. The incidence of tumors with any kind of neurohormonal peptide immunoreactive tumor cells was 53% in the trabecular carcinoids, and 42% in the strumal carcinoids, whereas the incidence was much lower (7%) in the insular type. Immunoreactive pancreatic polypeptide (PP), glucagon, enkephalin, and somatostatin were those neurohormonal peptides most commonly observed in the tumor cells of the primary carcinoids. Those less commonly found were substance P, calcitonin, VIP, neurotensin, beta-endorphin, and ACTH. Four metastatic carcinoids were nonreactive with all the antisera used. Cells storing immunoreactive insulin, glucagon, PP, VIP, gastrin, substance P, or enkephalin were found in one of the two remaining metastatic carcinoids; in the other only gastrin-immunoreactive tumor cells were observed. The occurrence and distribution of tumor cells storing the neurohormonal peptides in ovarian carcinoids are discussed in relation to their possible origin in the ovary and to carcinoids in the gut.

Carcinoid Tumor↗
PubMed1982

Substance P-immunoreactive nerve fibres in the anterior segment of the rabbit eye. Distribution and possible physiological significance.

Substance P-immunoreactive nerve terminals were found in several locations in the anterior segment of the rabbit eye. In the iris they occurred in the sphincter muscle and were randomly distributed in the iris stroma with some fibres running close to the dilator muscle. In the ciliary body these immunoreactive elements were few and occurred within bundles of nerve fibres. while in the ciliary processes they were more numerous with a predominantly subepithelial location. Blood vessels in the anterior uvea were often surrounded by substance P-immunoreactive fibres. No substance P-fibres were found in the cornea, while the sclera contained very few such elements. Using conventional in vitro techniques it was found that the sphincter pupillae muscle of the iris responded to electrical stimulation with a contraction that was resistant to cholinergic and adrenergic blockade, but was inhibited by the neuronal blocker tetrodotoxin. This indicates the existence of a non-cholinergic, non-adrenergic neuronal mediator of the contractile response. Exogenously applied substance P produced a long-lasting contraction of the spincter muscle, an observation compatible with the view that substance P is the noncholinergic, non-adrenergic neurotransmitter involved.

Animals↗
PubMed1982

The life cycle of the gastrin granule.

The ultrastructure of gastrin cells in the rat antrum was analyzed with standardized and quantitative planimetric methods. Resting and active cells were compared. The gastrin cells were activated by removal of the acid-producing part of the stomach (fundectomy). As a result of the serum gastrin concentrations were greatly elevated. Compared with gastrin cells in fasted control rats the gastrin cells in fundectomized rats were increased in number, contained fewer cytoplasmic granules, increased amount of endoplasmic reticulum, and an enlarged Golgi area. Generally, the secretory granules of the gastrin cell displayed a wide range of electron density from highly electron-dense to electron-lucent. They exhibited certain characteristic features: 1) Electron-dense granules made up a greater proportion of the total granule population in active gastrin cells than in resting cells. 2) Electron-dense granules were more frequent near the Golgi stacks than in the periphery of the cell. 3) Electron-dense granules were smaller in size than the electron-lucent granules; hence, small electron-dense granules probably represent young granules (progranules), while large, electron-lucent granules represent mature (old) granules. 4) Electron-dense granules invariably displayed a more intense immunoreactivity than electron-lucent granules. The gastrins are generated from a large precursor molecule. The post-translational processing of this precursor is reflected in the gastrin-component pattern. The gastrin-component pattern in antral extracts of fundectomized and normal fasting rats differed in that the proportion of the gastrin-4-like component was reduced, whereas the gastrin-34-like component was increased in the fundectomized rats. The results suggest a greater proportion of small gastrin components in the mature granules than in the newly formed ones, presumably due to more extensive conversion of larger forms into smaller forms with a longer granule half-life. As a result gastrin-17- and gastrin-34-like components make up a larger proportion of total gastrin in active gastrin cells than in resting gastrin cells.

Animals↗