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Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 145 records · Page 8Linked to original sources
PubMed1995

In vivo restitution of airway epithelium.

Epithelial shedding occurs in health and, extensively, in inflammatory airway diseases. This study describes deepithelialisation, reepithelialisation and associated events in guinea-pig trachea after shedding-like epithelial denudation in vivo. Mechanical deepithelialisation of an 800-microns wide tracheal zone was carried out using an orotracheal steel probe without bleeding or damage to the basement membrane. Reepithelialisation was studied by scanning- and transmission electron microscopy and light microscopy. Nerve fibres were examined by immunostaining. Cell proliferation was analysed by [3H]-thymidine autoradiography. Immediately after epithelial removal secretory and ciliated (and presumably basal) epithelial cells at the wound margin dedifferentiated, flattened and migrated rapidly (2-3 microns/min) over the denuded basement membrane. Within 8-15 h a new, flattened epithelium covered the entire deepithelialised zone. At 30 h a tight epithelial barrier was established and after 5 days the epithelium was fully redifferentiated. After completed migration an increased mitotic activity occurred in the epithelium and in fibroblasts/smooth muscle beneath the restitution zone. Reinnervating intraepithelial calcitonin gene-related peptide-containing nerve fibres appeared within 30 h. We conclude that (1) reproducible shedding-like denudation, without bleeding or damage to the basement membrane, can be produced in vivo; (2) secretory and ciliated cells participate in reepithelialisation by dedifferentiation and migration; (3) the initial migration is very fast in vivo; (4) shedding-like denudation may cause strong secretory and exudative responses as well as proliferation of epithelium, and fibroblasts/smooth muscle. Rapid restitution of airway epithelium may depend on contributions from the microcirculation and innervation.

Animals↗
PubMed1995

Presence and effects of pituitary adenylate cyclase activating peptide in the submandibular gland of the ferret.

Pituitary adenylate cyclase activating peptide (PACAP), a recently described vasoactive intestinal peptide-like neuropeptide, was found to be present in neurons in the submandibular gland of the ferret, where PACAP-immunoreactive nerve fibers were distributed around blood vessels, acini and ducts. Most of the PACAP-immunoreactive fibres were distinct from those storing vasoactive intestinal peptide. PACAP occurs in tissues as PACAP1-38 and PACAP1-27. PACAP1-38 and PACAP1-27 but not PACAP16-38 displayed biological activity with about the same potency. They exerted vasodilator effects on the submandibular vasculature, which resulted in a greater fall in vascular resistance than an equimolar dose of vasoactive intestinal peptide. The vasodilator response was independent of muscarinic receptor activation. Neither vasoactive intestinal peptide nor PACAP alone evoked any flow of saliva. However, both vasoactive intestinal peptide and PACAP enhanced the fluid response to acetylcholine, and the flow of saliva as well as the output of protein in response to parasympathetic nerve stimulation, vasoactive intestinal peptide being more potent than PACAP. In vitro, protein was released from submandibular gland tissue in response to both vasoactive intestinal peptide and PACAP, vasoactive intestinal peptide being more potent than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect following adrenoceptor and muscarinic blockade and following degeneration of sympathetic nerves. Sympathetic denervation combined with parasympathetic preganglionic denervation resulted in supersensitivity to both vasoactive intestinal peptide and PACAP. The fact that PACAP and vasoactive intestinal peptide occur in different nerve fibre populations suggests different roles for the two peptides in the submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine: a clue to Hirschsprung's disease.

The lack of nonadrenergic, noncholinergic (NANC) inhibitory innervation in aganglionic intestine is typical of Hirschsprung's disease. Several neuropeptides participating in the intestinal NANC innervation are greatly reduced in aganglionic intestine. However, these findings do not fully explain the pathophysiology of the disease. Recently, nitric oxide (NO) has been presented as a potent smooth muscle relaxant, and the enzyme responsible for its formation, nitric oxide synthase (NOS) has been demonstrated in neuronal elements in both the central and peripheral nervous system. In our study, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, a marker for NOS, and NOS immunohistochemistry revealed a dense innervation of the smooth muscle layers and the myenteric ganglia in ganglionic non afflicted intestine from patients with Hirschsprung's disease. By contrast, there was an almost complete lack of NOS-immunoreactive and NADPH-diaphorase-positive nerve fibers in the afflicted aganglionic bowel. NOS and vasoactive intestinal peptide were found to be partially colocalized in nerve fibers and neuronal cell bodies in the ganglionic but not in the aganglionic intestine. The lack of NO-producing nerve fibers in the aganglionic intestine probably contributes to the inability of the smooth muscle to relax, thereby causing lack of peristalsis in Hirschsprung's disease.

Amino Acid Oxidoreductases↗
PubMed1995

Epithelial pathways for luminal entry of bulk plasma.

Inflammatory challenges of the airway mucosa cause luminal entry of bulk plasma. Extravasation of plasma is well described but the routes for epithelial passage of plasma are largely unknown. Using colloidal gold (5 nm) as tracer we have now examined the fate of extravasated plasma in the airways. The tracer was given intravenously to anaesthetized, ovalbumin-sensitized guinea-pigs 2 min prior to airway mucosal challenge with 12 pmol ovalbumin (the dose was selected from a separate dose-response study). Tissue specimens were collected 30 s, 3 and 6 min after end of challenge (separate time course experiments suggested that the peak rate of entry of plasma occurred at about 5 min). The colloidal gold particles were visualized by autometallographic silver intensification. The gold produced no circulatory disturbance and had a uniform vascular distribution with negligible adherence to vascular endothelium. After challenge gold was first widely distributed in the lamina propria. At 3 and 6 min the tracer was also in the epithelium and airway lumen. It appeared that plasma was moved distinctly between and all around each epithelial cell. Bright field-, scanning-, and transmission electron-microscopy indicated that the luminal entry of plasma did not affect the integrity of the epithelial lining. This study demonstrates that the plasma exudate moves across an intact epithelial layer through ubiquitous paracellular pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1995

Changes in neuroendocrine elements in bronchial mucosa in chronic lung disease in adults.

BACKGROUND: It is not clear whether there is any association between metaplasia of the bronchial epithelium and changes in the distribution of neuroendocrine cells. This study examined, by immunohistological techniques, the distribution of neuroendocrine cells and juxtamucoscal nerve fibres in bronchial biopsies showing metaplastic changes. METHODS: Bronchial biopsies from 12 subjects with epithelial metaplasia associated with bronchiectasis and diffuse pulmonary fibrosis were examined by conventional light microscopy and immunohistological techniques for protein gene product 9.5 (PGP), chromogranin A and B (CAB), serotonin, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), calcitonin (CT), and gastrin releasing peptide (GRP). RESULTS: Regions of non-metaplastic epithelium contained numerous PGP and serotonin immunoreactive cells. Sub-populations of these cells displayed CAB, CGRP, CT, and GRP immunoreactivity. Metaplastic epithelium contained only a few weakly stained PGP, serotonin, CAB, GRP, CT and CGRP immunoreactive cells in six cases. Metaplastic epithelium was characterised by a high number of CAB-containing cells in six cases and in these biopsies prominent PGP-containing nerve bundles were seen in the subepithelial layer beneath the metaplastic epithelium. CONCLUSIONS: The distribution patterns of neuroendocrine cells and neuronal elements vary between areas of normal and metaplastic epithelium and within areas of metaplastic epithelium. Neuronal hyperplasia was associated with an increase in the number of CAB-containing cells within the metaplastic epithelium.

Adult↗
PubMed1995

Effects of topical budesonide on epithelial restitution in vivo in guinea pig trachea.

BACKGROUND: Continuous epithelial shedding and restitution processes may characterise the airways in diseases such as asthma. Epithelial restitution involves several humoral and cellular mechanisms that may potentially be affected by inhaled anti-asthma drugs. The present study examines the effect of a topical steroid on epithelial restitution in vivo in the guinea pig. METHODS: The airway epithelium was mechanically removed from well defined areas of guinea pig trachea without surgery and without damage to the basement membrane or bleeding. An anti-inflammatory dose of budesonide (1 mg) was administered repeatedly to the tracheal surface by local superfusion 24 hours before, at (0 hours), and 24 hours after the denudation. Migration of epithelial cells, formation of a plasma exudation-derived gel, and appearance of luminal leucocytes were recorded by scanning electron microscopy. Cell proliferation was visualised by bromodeoxyuridine immunohistochemistry and tissue neutrophils and eosinophils by enzyme histochemistry. RESULTS: Immediately after creation of the denuded zone ciliated and secretory cells on its border dedifferentiated, flattened out, and migrated speedily (mean (SE) 2.3 (0.3) micron/min) over the basement membrane. After 48 hours the entire denuded zone (800 microns wide) was covered by a tightly sealed epithelium; at this time increased proliferation was observed in new and old epithelium and subepithelial cells. Budesonide had no detectable effect on epithelial dedifferentiation, migration, sealing, or proliferation. Immediately after denudation and continuously during the migration phase plasma was extravasated creating a fibrinous gel rich in leucocytes, particularly neutrophils, over the denuded area. Budesonide had no effect on either the gel or the leucocyte density. CONCLUSIONS: These observations suggest that topical glucocorticoids may not interfere with a fast and efficient restitution of the epithelium in the airways.

Administration, Topical↗
PubMed1995

Administration of omeprazole to rats for one year produces reciprocal effects on antral gastrin and somatostatin cells and no effect on endocrine cells in the colon.

Inhibition of acid secretion with high doses of antisecretagogues, such as omeprazole, is known to raise the plasma gastrin levels. In the present study, we examined the effect of long-term (1-year) treatment of female rats with high doses of omeprazole on the density of antral gastrin and somatostatin cells. A possible effect on the endocrine cell density (chromogranin A as marker) and mucosal thickness of the colon was also examined. The plasma gastrin level in the omeprazole-treated rats was increased 15-fold compared with the level in the controls. The gastrin cell density, on the other hand, showed only a 2-fold increase. The somatostatin cell density in the omeprazole-treated rats was half that in the controls, indicating an inverse relationship between antral gastrin and somatostatin. In the colonic mucosa, neither the mucosal thickness nor the number of chromogranin-A-containing endocrine cells were affected by the omeprazole-induced hypergastrinemia. The results indicate that long-term acid inhibition results in a sustained hypergastrinemia, a modest and stable antral gastrin cell hyperplasia, antral somatostatin cell hypoplasia and lack of trophic effects in the colon.

Animals↗
PubMed1995

Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas.

There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.

Adenoma↗
PubMed1995

Innervation of the skin of the forearm in diabetic patients: relation to nerve function.

Complications of diabetes include sensory and autonomic neuropathy. The aim of the present paper was to study the degree of sensory and autonomic neuropathy and correlate these findings with the distribution and density of neuropeptidergic nerve fibers in the skin of the forearm of diabetic patients and healthy controls. We investigated 30 diabetics (24 type 1 and 6 type 2) and compared them with 13 healthy controls. There were no differences between the groups with respect to density and distribution of nerve fibers displaying immunoreactivity to the pan-neuronal marker PGP 9.5 and sensory and parasympathetic neuropeptides (substance P, calcitonin gene-related peptide and vasoactive intestinal peptide). By contrast, nerve fibers containing neuropeptide Y, a marker of sympathetic neurons, were reduced in number in the diabetic patients. C-fiber function (measured as the axon-reflex-evoked flare response) became impaired with increasing age in all subjects. The diabetic patients, however, showed a reduced flare compared to age-matched healthy controls. The reduction was particularly prominent in the younger patients (20-50 years). There was a greater reduction of the flare in neuropathic patients than in non-neuropathic patients, but there was no correlation between the degree of functional impairment and the duration of the disease.

Adult↗
PubMed1995

Trophic effects in the acid-producing part of the rat stomach after pyloric stenosis.

BACKGROUND: Pyloric stenosis produces gastric hypersecretion and is thought to stimulate the growth of the gastric mucosa in the rat, the dog, and man. However, the mechanisms behind the hypersecretion and the trophic effect of pyloric stenosis are little known. The purpose of the present study was to examine whether the postulated trophic effects described include growth of the histamine-producing enterochromaffin-like (ECL) cells and whether circulating gastrin can be held responsible. METHODS: Pyloric stenosis was produced in rats by tying a ligature around the pylorus, thereby narrowing the passage through the sphincter. The animals were left for 4 to 12 weeks. RESULTS: The operation dilated the stomach, increased the serum gastrin concentration approximately twofold, and increased the oxyntic mucosal weight, volume, and surface area but not the mucosal thickness and total DNA content. The interglandular space was increased, and the DNA concentration was reduced. The density of the ECL cells (that is, the number of ECL cells per visual field) was reduced at 4 weeks and back to control values at 8 and 12 weeks. The calculated total volume of the ECL cell population was unchanged at first but showed a less than twofold increase 12 weeks after the operation. The volume density of the ECL cells (that is, the proportion of the mucosa made up of ECL cells) was reduced at 4 and 8 weeks and was back to normal at 12 weeks. The ECL cells are rich in histidine decarboxylase (HDC); whenever the cells are stimulated, the enzyme activity increases. The HDC activity in the oxyntic mucosa was reduced at first and returned to control values 12 weeks later. CONCLUSIONS: Pyloric stenosis per se does not affect the total number of oxyntic mucosal cells, but causes the ECL cell population to grow somewhat, probably because of the moderate hypergastrinemia. Interestingly, however, there was no increase in the HDC activity, suggesting that the ECL cells are not much activated by the operation.

Animals↗
PubMed1995

Islet amyloid polypeptide (amylin) is expressed in sensory neurons.

Islet amyloid polypeptide (IAPP) or amylin is a hormone candidate predominantly expressed in insulin cells. A role for IAPP in the regulation of glucose homeostasis and the development of non-insulin-dependent diabetes mellitus has been proposed. IAPP is structurally related to the sensory neuropeptide calcitonin gene-related peptide. In the present study, using in situ hybridization, immunocytochemistry, and immunochemistry, the expression of IAPP in sensory neurons in the rat was investigated. IAPP was expressed in a population of small- to medium-sized nerve cell bodies in dorsal root ganglia from all levels and in the jugular-nodose and trigeminal ganglion; IAPP-expressing nerve cell bodies constituted a subpopulation of those expressing calcitonin gene-related peptide. In addition, IAPP-like immunoreactivity occurred in nerve cell bodies storing substance P and pituitary adenylate cyclase-activating polypeptide. IAPP-immunoreactive nerve fibers were encountered in the dorsal horns of the spinal cord, and to a lesser extent in peripheral tissues receiving sensory innervation; IAPP-immunoreactive fibers constituted a subpopulation of those containing calcitonin gene-related peptide and/or substance P. The immunochemical determinations demonstrated a low level of IAPP-like immunoreactivity in the dorsal root ganglia and spinal cord, which chromatographically coeluted with authentic rat IAPP. We conclude that IAPP is expressed in sensory neurons, thus being a novel sensory neuropeptide candidate for which a physiological role remains to be identified.

Amyloid↗
PubMed1995

[The localization of protein gene product 9.5 in the lungs of children with bronchitis and bronchiectasis].

Human respiratory tract has a rich innervation with nerve fibers. Presence and distribution of nerve elements labeled with protein gene product 9.5 (PGP) were studied in the lungs of children with bronchitis and bronchiectasis. Smooth myocytes, blood vessels and mixed glands of the walls of bronchi principales were surrounded with single PGP-positive nerve fibers in perichondrium grows smaller with age. Nerve fibers also surround lymph nodules of the bronchi principales mucosa. Small or medium number of them in nerve plexuses and surround basically blood vessels. As neuropeptide function in respiratory tract vary, they may be of certain importance in pathogenesis of chronic lung diseases. Morphological base of this suggestion was given.

Adolescent↗
PubMed1994

Localization of hormone-sensitive lipase to rat Sertoli cells and its expression in developing and degenerating testes.

Using in situ hybridization, hormone-sensitive lipase was found to be expressed in a stage-dependent manner in Sertoli cells of rat testis. No expression was found in Leydig cells but expression in spermatids could not be excluded. These results suggest a role for hormone-sensitive lipase in the metabolism of lipid droplets in Sertoli cells, in contrast to its previously proposed function in steroid biosynthesis. The expression of testicular hormone-sensitive lipase mRNA and protein, both larger in size compared to other tissues, coincided with the onset of spermatogenesis and was dependent on scrotal localization of the testis, suggesting a temperature-dependent, pretranslational regulation of expression.

Animals↗
PubMed1994

Immunocytochemical evidence for chromogranin A and B in neuronal elements in human gut.

Chromogranins are a family of acidic proteins known to occur in the secretory granules of endocrine cells and neurons in mammals. The aim of the present study was to investigate the possible neuronal localisation of chromogranins in human intestine and their relationship with other neuronal constituents using one antibody recognizing both chromogranin A and B (CAB) and others recognizing only chromogranin A. Immunoreactive CAB was found to occur in mucosal endocrine cells and in neuronal elements of all layers throughout human gut. A few to large number of CAB-immunoreactive nerve fibers were seen in smooth muscles as well as in submucous and myenteric ganglia and they were regularly found around blood vessels. Occasional CAB immunoreactive nerve cell bodies could be demonstrated in both submucous and myenteric ganglia indicating a local origin of some of the immunoreactive fibers. Most of these neurons seemed to lack acetylcholine esterase, and could be classified as non-cholinergic. CAB coexisted with the catecholamine-synthesizing enzyme tyrosine hydroxylase indicating the presence of chromogranins in noradrenergic nerve fibers. The presence of CAB-immunoreactive nerve cell bodies indicates that some CAB-containing fibers are intrinsic in origin. The distribution of chromogranin A and B immunoreactive nerve fibers in all layers of the gut wall suggests multiple targets for neuronal CAB, and/or their processing products.

Acetylcholinesterase↗
PubMed1994

Calcitonin, CGRP and helodermin in endocrine cells of the developing rat lung.

Calcitonin gene-related peptide (CGRP), calcitonin and immunoreactive helodermin occur in endocrine cells in the murine airways. In the lungs these cells form clusters, while they occur scattered in the larynx and trachea. In the present study of the developing rat CGRP-immunoreactive cells were more numerous at all stages than the calcitonin- and helodermin-containing ones. A subpopulation of the CGRP-containing cells contained either calcitonin or helodermin. Immunocytochemistry revealed a higher density of CGRP-containing endocrine cells in the lungs of fetal and newborn rats than in the lungs of older rats, while the density of calcitonin-containing cells was largely unchanged. The helodermin-containing cells were few at all developmental stages examined. The concentration and content of CGRP were highest in newborn rats; the levels decreased postnatally. The calcitonin concentration did not change during development while the content increased with age. The concentration and content of helodermin increased with age.

Aging↗
PubMed1994

Peptide-containing nerve fibers in the parathyroid glands of different species.

Several neuropeptides, calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), vasoactive intestinal polypeptide (VIP), the noradrenergic marker dopamine beta-hydroxylase (DBH) and the general neuroendocrine marker PGP 9.5 were localized by immunocytochemistry in the parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep. The general density of innervation varied markedly among the species. Nerve fibers storing CGRP, NPY, PACAP, SP and VIP were present in all species examined. Galanin-containing fibers occurred in all species except guinea-pig and adrenergic (DBH-containing) fibers in all species except chicken and guinea-pig. Generally, the nerve fibers were distributed around blood vessels, in the parenchyma as single scattered fibers, and often also within the capsule. Coexistence studies were performed in cat and sheep. CGRP and SP invariably coexisted in the same nerve fibers. Further, CGRP partially coexisted with PACAP, NPY was observed in the same nerve fibers as DBH. A small population of NPY-containing fibers also seemed to contain galanin (cat only). VIP and NPY coexisted in a population of nerve fibers in the parenchyma. A population of VIP-containing fibers also seemed to contain PACAP. The results indicate the presence of several neuropeptides in the parathyroid glands. As judged by their distribution patterns they may regulate both secretory activity and blood flow, some of them possibly in a cooperative manner.

Animals↗