Search PubMed⌕ Search

Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

627 records · Page 35Linked to original sources

Beta-microseminoprotein in gastric carcinoids: a marker of tumour progression.

Gastric carcinoid disease may have a highly varying clinical course depending on the malignancy of the tumour. Many biochemical markers, such as peptides and biogenic amines, have been found in carcinoid tumour tissue but none has been reported to be useful as a predictor of the degree of malignancy of the carcinoid. beta-Microseminoprotein is a small disulphide-rich protein with unknown function present in the secretions on most mucosal surfaces in the body, including the stomach where it is also found in some endocrine cells. We have studied beta-microseminoprotein by immunohistochemistry in the tumour tissue of 29 patients with gastric carcinoid disease. Beta-Microseminoprotein was present in the tumour tissue in 62% of the patients and its presence was correlated to tumour diameter and tissue invasion depth. The presence of beta-microseminoprotein in tumour tissue was corroborated by in situ hybridisation. All 4 patients with the solitary sporadic type of tumour and all 6 patients with metastasis had positive immunostaining of the tumour tissue. The serum concentration of beta-microseminoprotein, measured by radioimmunoassay, was increased in all but 2 of 13 patients with gastric carcinoid disease. To a large part the increase was due to the concomitant atrophic corpus gastritis. We conclude that beta-microseminoprotein in tumour tissue is a marker of tumour progression and that measurement of beta-microseminoprotein in serum is less informative than immunohistochemistry.

Adult↗

Innervation of the feline eustachian tube.

The distribution of adrenergic, cholinergic and peptidergic nerves in the feline eustachian tube was studied using histochemical techniques. Adrenergic, acetylcholinesterase-positive and vasoactive intestinal polypeptide immunoreactive nerves were numerous in the tubal wall. All three types of nerve fibers occurred in the subepithelial layer, around small blood vessels and around the acini of seromucous glands. No nerves displaying substance P or enkephalin immunoreactivity were observed.

Acetylcholinesterase↗

Autonomic innervation of the middle ear.

The distribution of nerve fibers in the middle ear mucosa and eardrum of the cat and guinea pig was studied using immunocytochemical and histofluorescence techniques. Nerve fibers containing noradrenaline, vasoactive intestinal peptide, substance P, enkephalin or immunoreactive avian pancreatic polypeptide were demonstrated in the middle ear mucosa. After extirpation of the superior cervical ganglion, nerve fibers containing noradrenaline and avian pancreatic polypeptide disappeared while fibers containing vasoactive intestinal peptide, substance P and enkephalin seemed to remain unaffected.

Adrenergic Fibers↗

Occurrence and distribution of VIP nerves in the nasal mucosa and tracheobronchial wall.

Nerves displaying vasoactive intestinal peptide (VIP) immunoreactivity were detected in the upper respiratory tract of guinea pigs, rabbits and cats. VIP nerves were numerous in the cat, less numerous in the rabbit and rare in the guinea pig. In the nasal mucosa, fine varicose VIP nerves were found to surround nasal glands and small blood vessels. In the tracheobronchial wall VIP nerves were observed around seromucous glands, blood vessels and smooth muscle. Ganglia located in the walls of the trachea and main bronchi contained clusters of VIP immunoreactive nerve cell bodies, conceivably representing the origin of the VIP fibres found in this region.

Animals↗

The origin of vasoactive intestinal polypeptide (VIP) nerves in the feline nasal mucosa.

The feline nasal mucosa is richly supplied with vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. The nerves occur in the subepithelial connective tissue, around small blood vessels and around the acini of seromucous glands. The ptergopalatine ganglion contains numerous VIP immunoreactive nerve cell bodies among non-reactive ones. Extirpation of the ganglion results in an almost complete disappearance of VIP-containing nerves in the nasal mucosa, while sectioning of the preganglionic nerve (Vidian nerve) does not affect the number of nasal VIP nerves. Hence the bulk of VIP nerve fibers in the nasal mucosa derive from cell bodies located in the pterygopalatine ganglion.

Animals↗

Effects of vasoactive intestinal polypeptide on resistance and capacitance vessels in the nasal mucosa.

Vasoactive intestinal polypeptide (VIP) immunoreactive nerves have previously been demonstrated in the feline nasal mucosa. In the present investigation it is shown that VIP given close arterially dilates both resistance and capacitance vessels in the nose of the cat. This vasodilatation is atropine resistant. It is suggested that VIP serves a physiological role in the neurogenic control of blood vessels in the nasal mucosa.

Animals↗

Ontogeny of ECL cells in the rat.

ECL cells produce histamine and chromogranin A, and are restricted to the oxyntic mucosa of the stomach. ECL cell ontogeny has been studied in some detail in the rat. Using histidine decarboxylase immunostaining, the first ECL cells can be demonstrated at embryonic day 17. Immunoreactive histamine and chromogranin A appear one day later. At embryonic day 20, the vesicular monoamine transporter type 2 is also present in the ECL cells. Neonatally the ECL cell proliferation is slow; however, one to three weeks postnatally there is a rapid growth of ECL cells to populate the basal half of the glands. Gastrin is known to be an important stimulator of ECL cell activity and growth in the adult rat. As revealed in recent mouse gene knock out models gastrin does not seem to play a role in the early ECL cell differentiation and development.

Animals↗

Physiological significance of ECL-cell histamine.

In the oxyntic mucosa of the mammalian stomach, histamine is stored in ECL cells and in mucosal mast cells. In the rat, at least 80 percent of oxyntic mucosal histamine resides in the ECL cells. Histamine is a key factor in the regulation of gastric acid secretion. Following depletion of ECL-cell histamine by treatment with alpha-fluoromethylhistidine (alpha-FMH), basal acid secretion was reduced, and gastrin-stimulated acid secretion was abolished. Vagally-induced acid secretion (by insulin injection or pylorus ligation) was unaffected by alpha-FMH treatment but inhibited by an H2 antagonist. These results suggest that gastrin stimulates acid secretion via release of ECL-cell histamine, whereas vagally-induced acid secretion--although histamine-dependent--does not rely on ECL-cell histamine. Gastrin is known to have a trophic effect on the oxyntic mucosa. By combining long-term hypergastrinemia with continuous infusion of alpha-FMH, we were able to show that gastrin-evoked trophic effects in the stomach do not depend on ECL-cell histamine.

Animals↗

The biology and pathobiology of the ECL cells.

The enterochromaffin-like (ECL) cells represent the predominant endocrine cell population in the acid-producing part of the stomach of both experimental animals and man. These cells actively produce and store histamine in addition to an anticipated but as yet unidentified peptide hormone and are under the control of gastrin. An acute gastrin stimulus causes exocytosis of the cytoplasmic granules/vesicles (and release of histamine and activation of the histamine-forming enzyme, histidine decarboxylase), while a more sustained gastrin stimulus causes first hypertrophy and then hyperplasia of the ECL cells in the rat (at most, a fivefold increase in the cell number). These effects can be demonstrated following infusion of gastrin or following an increase in the concentration of circulating gastrin of endogenous origin. The growth of the ECL cells reflects an accelerated self-replication rate. As studied in the rat, the self-replication rate is accelerated quite soon after induction of hypergastrinemia (blockade of acid secretion), the rate is maximally elevated within two weeks and then declines to control values at ten and 20 weeks despite the sustained hypergastrinemia. Lifelong hypergastrinemia in rats is associated not only with ECL-cell hyperplasia but also with an increased incidence of ECL-cell carcinoids. Recently, we could show that alpha-fluoromethylhistidine, which is a suicide inhibitor of histidine decarboxylase, effectively depletes the ECL cells of histamine and that the histamine-depleted ECL cells respond to gastrin with hyperplasia in a manner identical to normal ECL cells. Other factors beside gastrin seem to participate in the control of ECL-cell function and proliferation. Although exogenous somatostatin is known to suppress the activity of the ECL cells, we have failed to obtain evidence that the somatostatin cells in the oxyntic mucosa play a role in the physiological control of the ECL cells. The vagus, however, is important for the ability of the ECL cells to respond to gastrin. This conclusion is based on the observation that vagal denervation suppresses the hyperplastic response of the ECL cells to gastrin. Porta-cava shunting, on the other hand, greatly enhances the responsiveness of the ECL cells to gastrin. The mechanism behind this effect is unknown.

Animals↗

Fluorescamine in cytodiagnosis of thyroid carcinomas.

Fluorescamine, which reacts with primary amino groups yielding intensely fluorescent products, was found to induce intense fluorescence in cells from medullary and papillary thyroid carcinoma. No fluorescence was detected in cells from follicular or undifferentiated carcinoma or from benign thyroid lesions, except Hürthle cell adenomas, the cells of which exhibited moderate fluorescamine-induced fluorescence. This was demonstrated on fine needle aspiration biopsy smears pretreated with formaldehyde gas. Since the fluorescamine technique is simple and rapid, it may be of value as an aid in the cytodiagnosis of thyroid neoplasms.

Biopsy, Needle↗

Fluorescamine as a cytochemical detection reagent for mammary carcinoma cells.

Fluorescamine is a versatile reagent for the cytochemical demonstration of primary amino groups. Following pretreatment with formaldehyde, only certain "protected" amino groups will react with fluorescamine. In the present study we show that compounds containing such amino groups are abundant in mammary carcinoma cells but undetectable in normal mammary gland cells. Most cytologically benign breast lesions are devoid of cells containing these compounds. Although much work remains to be done, the fluorescamine technique, which is rapid and simple to perform, may offer some help in the distinction between normal and malignant cells of the mammary gland.

Breast Diseases↗

The biology and physiology of the ECL cell.

The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell type in the acid-producing part of the vertebrate stomach, are characterized by numerous, electron-lucent vesicles and few electron-dense granules in the cytoplasm. The biological and physiological significance of the ECL cells remains poorly understood. They produce and store histamine and pancreastatin and are thought to produce an as yet unidentified peptide hormone. The most important clue to their function is their willingness to respond to changes in circulating gastrin. The present review presents current knowledge of the biology and physiology of the rat stomach ECL cells. Examination of serially sectioned ECL cells has revealed that the cytoplasmic vesicles almost invariably contain an electron-dense core, suggesting that perhaps the distinction between granules and vesicles is artificial. We propose a life cycle of the secretory organelles in the ECL cells with a progressive development from granules to vesicles. The results showed that the gastrin-evoked release of histamine and pancreastatin was accompanied by loss of vesicles, and that synthesis of histamine and pancreastatin was accelerated by sustained infusion of gastrin, a treatment that was associated with renewal of vesicles. The events described are instrumental in bringing about a change in the "steady state" or "equilibrium" of the ECL cells, from a non-stimulated, resting state to a gastrin-stimulated, active state. This change is attained within six to eight hr. The next "steady state" change is that from "normal-sized" but active ECL cells to "hypertrophic" ECL cells. The increase in cell size is complete after about one week. The gastrin-evoked increase in the ECL cell self-replication rate is maximal after about 10 days, after which time there is a gradual return back to pre-stimulation values. The ECL cell density increases fairly slowly and does not reach maximum (four-fold increase) until after 20 weeks hypergastrinemia. The activity of the histamine-forming enzyme, histidine decarboxylase, is elevated by gastrin and remains elevated for as long as the gastrin stimulus is maintained (the longest time studied was 20 weeks). The physiological significance of the ECL cells is probably related to their capacity to produce and store histamine and an as yet unidentified peptide hormone. The ECL cells are thought to be the source of histamine necessary for the gastrin-evoked acid response. In addition, preliminary evidence suggests that the ECL cells and the anticipated ECL cell hormone play a role in bone formation.

Animals↗

Neuropeptides in the human penis: an immunohistochemical study.

In the present study, the distribution of neuropeptides in the human penis is demonstrated by immunohistochemistry (IHC). IHC screening detected a complex network of nerve fibers containing vasoactive intestinal polypeptide (VIP), peptide histidine-methionine (PHM), prepro-VIP (111-122), neuropeptide Y (NPY), C-flanking peptide of NPY (C-PON), calcitonin gene-related peptide, substance P, and galanin immunoreactivities. Special attention was also given to the recently isolated, VIP-related lizard peptide helospectin, which could also be detected in neuronal elements in the penis. Colocalization studies showed the coexistence of VIP, PHM, and partly helospectin, and of NPY with C-PON within nerve fibers in the cavernous and spongious body, the glans penis, and the urethra.

Adult↗

Tissue concentrations of gastrointestinal regulatory peptides in the duodenal mucosa in systemic sclerosis.

OBJECTIVE: Esophageal hypomotility and abnormalities of intestinal function are important manifestations in systemic sclerosis (SSc), but their pathogenesis is not well understood. Since there is evidence that plasma concentrations of certain gastrointestinal regulatory peptides are increased in SSc, we were interested in examining the peptide concentrations and localization in biopsy specimens from the intestinal mucosa in SSc patients. We studied 12 patients with gastrointestinal disease. METHODS: Levels of corticotrophin-releasing hormone (CRH), motilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC), and the occurrence of motilin, PYY, somatostatin, and NPY were studied with immunohistochemistry. RESULTS: Except for the concentrations of CRH, which were increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased by approximately 50% among patients with esophageal and intestinal dysfunction (group B) compared to patients with impaired esophageal motility alone (group A). In addition, HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments among patients in groups A and B. In all patients duodenal motilin, PYY, and somatostatin were localized in the endocrine cells. The distribution and frequency of the cells did not differ among the patients. NPY was localized to neuronal elements; there was no overt difference among the patients with respect to the frequency of NPY-containing nerves. CONCLUSION: This study shows that patients with widespread gastrointestinal disease have lower tissue concentrations of regulatory peptides compared to patients with less widespread disease.

Adult↗