Biomedical subjects

S Forsgren

Publications and source records attributed to S Forsgren.

At least 73 records · Page 4Linked to original sources

PubMed1992

Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland.

Substance P and calcitonin gene-related peptide (CGRP) are present in nerve fibers innervating the submandibular gland. Radiotherapy of tumors in the head and neck region usually embraces the salivary glands in the irradiated field and consequently a dramatic decrease in salivary function is seen. In this study, the submandibular glands and ganglia of rats subjected to fractionated irradiation were examined by use of immunohistochemical techniques for demonstration of substance P and CGRP. Irradiation was given on five consecutive days (daily doses of 6-9 Gray) with unilateral or bilateral irradiation techniques. Specimens of control and experimental animals were processed in parallel. A marked increase in the expression of substance P in the ganglionic cells--presumably parasympathetic--and in the number of fibers showing substance P-like immunoreactivity in association with acini and small ducts was seen in response to bilateral irradiation. (Surprisingly, unilateral irradiation of the parotid area had no effect on peptide distribution in the irradiated gland and ganglion). No changes in the pattern of CGRP immunoreactivity occurred. In the trigeminal ganglion, which supplies the submandibular gland with the majority of the sensory substance P- and CGRP-containing nerve fibers, no changes in the expression of substance P or CGRP immunoreactivity were seen. The results suggest that bilateral irradiation leads to an increase in the synthesis of substance P-like substance in the parasympathetic ganglionic cells supplying the submandibular gland with secretory nerves, and can thus be an additional factor in explaining the altered secretory capacity of salivary glands.

Animals↗

PubMed1992

Long-term hypoxia induces changes in the substance P immunoreactivity pattern in laryngeal nerve paraganglia.

We previously showed that long-term hypoxia increases the dopamine content in rat laryngeal nerve paraganglia. In the present study paraganglia of rats exposed to hypoxia (10 +/- 0.5% O2) for 14 days were examined immunohistochemically to detect changes in the expression of neuropeptides and catecholamine-synthesizing enzymes. Hypoxia induced an intense cellular substance P (SP)-like immunoreactivity (LI) in some paraganglia and an increase in the number of stromal nerve fibers showing SP-LI in others. The patterns of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, phenylethanolamine-N-methyltransferase-, vasoactive intestinal polypeptide-, neuropeptide-Y and calcitonin gene-related peptide-LI were not changed in response to hypoxia. The results show that hypoxia induces changes in the pattern of SP immunoreactivity in laryngeal nerve paraganglia and may indicate that SP plays a role in the regulation of catecholamine metabolism in this tissue.

Animals↗

PubMed1991

The phenotype of lymphoid cells and thymic epithelium correlates with development of autoimmune insulitis in NOD in equilibrium with C57BL/6 allophenic chimeras.

The mechanisms contributing to the development of autoimmune insulin-dependent diabetes mellitus have been analyzed in allophenic mouse chimeras of the NOD in equilibrium with C57BL/6 strain combination (where NOD is nonobese diabetic). Occurrence of lymphoid cell infiltration (insulitis) in pancreatic islets was observed in the majority of such chimeras. The development of insulitis was found to correlate with major histocompatibility complex chimerism in lymphoid cells and in thymus cortical regions. Chimeras with more than 50% of C57BL/6 lymphoid cells rarely developed insulitis. Our data suggest that the correlation with the thymic cortical region is absolute. Thus, all individuals displaying NOD or NOD/C57BL/6 thymic cortical regions developed insulitis, whereas we have not observed insulitis in chimeras with only C57BL/6 thymic cortical regions. Thus the positive selection of T cells appears to play a crucial role in the development of insulin-dependent diabetes mellitus.

Animals↗

PubMed1991

Enkephalin-like immunoreactivity in ganglionic cells in the larynx and superior cervical ganglion of the rat.

The distribution of enkephalin-like immunoreactivity (ENK-LI) in the larynx, the superior cervical ganglion (SCG) and the nodose ganglion of adult rats was examined in the present study. A substantial number of the local acetylcholinesterase (AChE)-positive, presumably parasympathetic, ganglionic cells in the larynx displayed ENK-LI. These cells also exhibited neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-LI. Varicose nerve fibers showing ENK-LI were observed close to the acini and ducts of the glands, in the perichondrium and in the lamina propria. The varicosities exhibiting ENK-LI frequently displayed NPY- and VIP-LI. The ENK-LI was detected in a subpopulation of AChE-positive nerve fibers in the laryngeal tissue. In the SCG, only a small number of the ganglionic cells displayed ENK-LI. These cells, in contrast to other ganglionic cells of the SCG, did not show NPY-LI. None of the ganglionic cells of the nodose ganglion exhibited ENK-LI. Sympathectomy and vagotomy affected neither the number nor the distribution of fibers showing ENK-LI in the larynx. In conclusion, ENK appears to be present together with NPY and VIP in the parasympathetic innervation of the larynx and in a very limited number of the ganglionic cells of a sympathetic ganglion, the SCG, of the adult rat.

Acetylcholinesterase↗

PubMed1991

Regional differences in the distribution of nerve fibers showing substance P- and calcitonin gene-related peptide-like immunoreactivity in the rat larynx.

The distribution of substance P (SP) - and calcitonin gene-related peptide (CGRP) - containing nerve fibers in the rat larynx was studied using immunohistochemistry. Double-labeling studies revealed a high degree of co-existence of SP- and CGRP-like immunoreactivity (LI) in the nerve fibers in the larynx. There was a considerable regional difference in the number of immunoreactive nerve fibers in the epithelium and lamina propria. Richly supplied sites were the laryngeal side of the epiglottis and the ventral recess, whilst there was no evidence of nerve fibers in the squamous epithelium of the vocal cords. However, where the squamous epithelium of the vocal cords changed into a cuboidal epithelium, a moderate number of nerve fibers was present, and a large number of fibers was seen where the squamous epithelium of the cords was in close contact with cartilage. Nerve fibers showing SP- and CGRP-LI were also observed close to the acini and ducts of the glands, in the blood vessel walls, close to the perichondrium of all the cartilages, and outside the cricothyroid and cricoarytenoid joints. CGRP-LI was detected in epithelial cells facing the lumen of the airway and in cells in the acini and ducts of glands in the subglottic region and trachea. Unilateral sympathectomy did not affect the pattern of SP- and CGRP-innervation in the larynx, whereas after vagotomy, the SP- and CGRP-innervation almost disappeared ipsilaterally in the upper parts of the epiglottis and aryepiglottic folds.

Animals↗

PubMed1991

Studies on colocalization of neuropeptide Y, vasoactive intestinal polypeptide, catecholamine-synthesizing enzymes and acetylcholinesterase in the larynx of the rat.

In the present immunohistochemical study, the distribution of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in the larynx was examined and compared with that of fibers containing tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), and with that of acetylcholinesterase (AChE)-positive nerve fibers, in intact and vagotomized rats and in rats subjected to removal of the superior cervical ganglion (SCG). Fibers showing TH/DBH-like immunoreactivity (LI) were only found in the walls of arteries and arterioles, whereas AChE-positive nerve fibers were located close to the acini and ducts of the glands, in blood vessel walls, in the perichondrium and in the lamina propria. NPY-LI and VIP-LI coexisted in local AChE-positive ganglionic cells and in a subpopulation of the AChE-positive fibers, NPY-LI also being present in some periarterial fibers showing TH/DBH-LI. Unilateral removal of the SCG eliminated the TH/DBH-innervation in the upper but not the lower parts of the larynx ipsilaterally, whereas the NPY-innervation of the arteries in the upper parts only partly disappeared and the NPY-innervation of the other structures remained unchanged. The distribution of VIP-innervation was unchanged after vagotomy and removal of the SCG. The results suggest that VIP is present in the postganglionic parasympathetic innervation, whereas NPY is present in both the postganglionic parasympathetic and sympathetic innervation of the rat larynx.

Acetylcholinesterase↗

PubMed1991

Transection of carotid sinus nerve inhibits the turnover of dopamine and norepinephrine in long-term hypoxic carotid bodies: a biochemical and morphometric study.

To assess the efferent influence of the carotid sinus nerve on the catecholamine function and the vascularity in long-term hypoxic carotid bodies, rats were exposed to hypoxia (10% O2 in nitrogen for 1 and 3 weeks) after unilateral transection of the sinus nerve. In the intact carotid bodies, long-term hypoxia elicited several biochemical and morphological alterations: increased turnover of dopamine and norepinephrine, increased volume density of blood vessels, decreased volume density of glomic tissue. Transection of the sinus nerve reduced but did not abolish the increase in turnover of dopamine and norepinephrine evoked by hypoxia without preventing the structural alterations. Immunocytochemical studies revealed the presence of nerve fibres exhibiting neuropeptide Y-like immunoreactivity which persisted after the excision of the carotid sinus nerve. Nerve fibres showing substance P-like immunoreactivity were found in the intact carotid bodies but not in the carotid bodies deprived of sinus nerve. It is concluded that the sinus nerve exerts a stimulatory efferent control on the synthesis and release of dopamine and norepinephrine in rat carotid body during long-term hypoxia, but no appreciable vasodilatory influence on the glomic vasculature. A possible role of substance P contained in the endings of the carotid sinus nerve is discussed.

Animals↗

PubMed1991

Monoclonal, natural antibodies prevent development of diabetes in the non-obese diabetic (NOD) mouse.

The development of diabetes in the non-obese diabetic (NOD) mouse is mediated by T cells of both the CD4+CD8- and CD4-CD8+ phenotypes, while B cells are not involved in the effector stage of the disease. We have recently found, however, that treatments with heterologous, polyclonal immunoglobulin (Ig) preparations, as well as suppressing the developing B cell repertoire for the first 4 weeks of life dramatically reduce the incidence of disease and the severity of insulitis, in treated mice. We have further investigated the influence of Igs on the development of autoimmunity by testing the effect of polyclonal mouse-Ig or monoclonal, natural antibodies derived from normal, neonatal BALB/c mice. We found that repeated administration of high doses of polyclonal Ig (of xenogenic or isogenic origin), given at birth, inhibits the development of insulitis, as well as diabetes. Furthermore, single injections of moderate doses of isogenic, natural monoclonal antibodies (mAb) administered at the same age, while failing to significantly alter the degree of insulitis, efficiently prevent the development of disease. The effect of mAbs was found to be related to V-region specificity, as only some mAbs of a given isotype and origin had the observed effect.

Animals↗

PubMed1991

Immunoglobulin-mediated prevention of autoimmune diabetes in the non-obese diabetic (NOD) mouse.

We investigated whether the development of spontaneous T-cell-mediated type I diabetes in NOD mice is influenced by B cells and immunoglobulin (Ig). During the first 4 weeks of life, B-cell development was suppressed by repeated administration of rabbit anti-mouse IgM (RaIgM), while controls received polyclonal rabbit Ig (NRIg). A reduction in the incidence of diabetes, as well as in development of insulitis, was observed after either of these treatments. However, the effect on insulitis was more pronounced in mice treated with RaIgM compared with those treated with NRIg. Furthermore, while the optimal effect of NRIg was obtained after a single injection at birth, the additional effect of RaIgM on development of insulitis was observed only after continued treatment for the first 4 weeks of life. Taken together these data suggest a possible role of Ig/B cells in the development of autoimmunity in the NOD mouse. The additional effect observed after continued suppression of the neonatal B-cell development suggests that this population may contribute significantly to the establishment of an auto-aggressive lymphocyte repertoire in the NOD mouse.

Animals↗

PubMed1991

Occurrence of mast cells in relation to the distribution of nerve fibers in the rat larynx.

The distribution of mast cells in the rat larynx was studied at a light microscopic level in relation to nerve fibers showing substance P (SP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) and ultrastructurally in relation to unmyelinated nerve fibers. Connective tissue mast cells (CTMC), demonstrated by staining for avidin-peroxidase and immunohistochemical staining for 5-hydroxytryptamine (5-HT), were localized in the lamina propria. Alcian blue and toluidine blue revealed mast cells in the epithelium and the lamina propria. The mast cells showed similar regional differences in their distribution as fibers showing SP- and CGRP-LI. A large or moderate number of cells was found on the laryngeal side of the epiglottis, in the ventral recess and in the aryepiglottic folds. No mast cells were found in the vocal cords. In addition, a large number of cells showing 5-HT-LI were observed in the subglottic epithelium but not in the supraglottic and the glottic epithelia. Ultrastructurally and by use of SP- and CGRP-immunohistochemistry, nerve fibers were sometimes observed close to the mast cells. These findings may be of importance in the understanding of laryngeal pathophysiological events.

Animals↗

PubMed1990

Catecholaminergic and peptidergic nerve components of intramural ganglia in the rat heart. An immunohistochemical study.

Immunohistochemical properties of the terminal nerve network in the rat heart were assessed by use of the elution-restaining method. The colocalization of the enzymes involved in catecholamine synthesis (tyrosine hydroxylase--TH. dopamine-beta-hydroxylase--DBH) as well as the respective distributions of the neuropeptides associated with the adrenergic nervous system (neuropeptide tyrosine--NPY, C-terminal flanking peptide of neuropeptide Y--C-PON) were studied in series of serial sections throughout the interatrial septum and the atrioventricular junction. Our data suggest that ganglion cells of sulcus terminalis as well as the epicardial ganglia enclosed between the superior vena cava and ascending aorta are VIP- and TH-negative, but neuropeptide Y- and DBH-immunoreactive. They give rise to three intraseptal nerves directed towards the specialised structures of the atrioventricular junction. These nerve fascicles contain abundant, thick TH-immunoreactive nerve fibres and scarce, thin NPY- and DBH-immunoreactive fibres. The cell bodies of the intramural ganglion cells localized between the right and left branches of the bundle of His (Moravec and Moravec 1984) are strongly TH- and DBH-immunoreactive. They are innervated by thick nerve fibres having the same immunohistochemical properties (NPY- and DBH-immunoreactivities) as those of a subpopulation of the epicardial ganglion cells and seem to supply some of the TH-immunoreactive nerve fibres directed via the intraseptal nerves to the epicardial ganglia. The existence of a multicomponent nerve network, characterized by a reciprocal innervation of the sinus node and atrioventricular node areas, is suggested by our immunohistochemical data.

Animals↗

PubMed1990

Catecholamine-synthesizing enzymes and neuropeptides in rat heart epicardial ganglia; an immunohistochemical study.

The subepicardial atrial ganglia of rat hearts were examined using immunohistochemical techniques and antibodies against the catecholamine-synthetic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and met-5-enkephalin (ENK). Some of the ganglion cells present in the ganglia exhibited DBH-like immunoreactivity (LI) and NPY-LI, whilst these cells never exhibited TH-, VIP-, CGRP-, SP- or ENK-LI. Groups of small cells exhibiting an intense TH-LI, corresponding to cells referred to as catecholamine-containing cells and sometimes small intensely fluorescent cells in the literature, were observed in the ganglia. A subpopulation of these cells exhibited immunoreactivity to one of the neuropeptides tested, namelyu SP. Only a few of the cells showing TH-LI displayed DBH-LI. Nerve fibres showing SP-, CGRP-, DBH- and TH-LI were present in the ganglia; some of these fibres being closely associated with the ganglion cells or with the cells showing TH-LI. The observation provide new information on the catecholamine-synthetic enzyme/neuropeptide expression of the ganglion and catecholamine-containing cells and of the associated nerve fibres of rat heart subepicardial ganglia.

Animals↗

PubMed1989

Vasoactive intestinal polypeptide-like immunoreactivity in the bovine heart: high degree of coexistence with neuropeptide Y-like immunoreactivity.

It is not known whether VIP coexists with other neuropeptides or neurotransmitters in the heart. In the present study, the distribution of nerve fibers showing VIP-like immunoreactivity (VIP-LI) in various parts of the bovine heart was compared with that of fibers possessing neuropeptide Y (NPY)- and dopamine-beta-hydroxylase (DBH)-LI. It was found that fibers showing VIP-LI most regularly occurred in the regions of sinuatrial and atrioventricular nodes and intracardiac ganglia, the nerve fibers being associated with nodal and ganglionic cells and arterial walls. Furthermore, it was observed that almost all fibers showing VIP-LI also exhibited NPY-LI. The fibers displaying VIP-LI occurred close to fibers endowed with DBH-LI, and on some occasions it appeared that varicosities showing immunolabeling for VIP also displayed DBH-LI. VIP- and NPY-LI, but not DBH-LI, was detected in some of the intracardiac ganglionic cells. The observations are discussed in relation to the previously known distribution and function of VIP in the heart and other organs. Further studies examining the effects of VIP and NPY in the heart should take into account possible interactions between these two peptides.

Animals↗

PubMed1989

The distribution of nerve fibers showing substance P-like immunoreactivity in the conduction system of the bovine heart: dense innervation in the atrioventricular bundle.

There is limited information on the distribution of nerve fibers containing substance P (SP) in the heart conduction system. Therefore, in the present study, the various parts of the conduction system of the bovine heart were examined by the use of an SP-antiserum and immunohistochemistry. Nerve fibers showing SP-like immunoreactivity (SP-LI) occurred in the proximities of conduction cells in all parts of the conduction system, but were present in greatly larger numbers in the AV bundle than in the other parts. The nerve fibers showed a predilection for certain regions of the bundles of conduction cells (Purkinje fiber bundles) in the AV bundle and the bundle branches and their ramifications. Nerve fibers showing SP-LI also occurred in the walls of the arteries and in association with some the ganglionic cells located in the regions of the conduction system. None of the ganglionic cells exhibited SP-LI. The observations are discussed in relation to what is known of the function of SP in the heart and of the distribution of sympathetic and parasympathetic nerve fibers in the conduction system. As SP is regarded as a marker of afferent fibers the observations support the view that afferent nerve fibers are present throughout the conduction system. It is likely that the existence of a significant SP-innervation in the conduction system is of importance for the function of this part of the heart.

Afferent Pathways↗

PubMed1989

Neuropeptides in intact and denervated tympanic membranes. An immunohistofluorescence study in the rat.

The distribution and origin of peptide-containing and sympathetic nerve fibers were studied in the tympanic membrane of rats with intact innervation, and in rats following sympathectomy, vagotomy, or capsaicin treatment. Nerve fibers showing substance-P-like immunoreactivity (SP-LI), calcitonin gene-related peptide (CGRP)-LI, vasoactive intestinal polypeptide (VIP)-LI, enkephalin-LI, neuropeptide Y (NPY)-LI and tyrosine hydroxylase (TH)-LI were detected along blood vessels in the pars flaccida, the external auditory canal and in the fibrocartilaginous ring of the pars tensa. In the pars flaccida there were numerous fibers demonstrating SP-LI and CGRP-LI, while there were few such fibers in the pars tensa. In both portions of the tympanic membrane these fibers were present within and beneath the keratinized stratified squamous epithelium. In the pars flaccida, nerve fibers showing SP-LI and CGRP-LI were also seen near mast cells. Sympathectomy led to a loss of nerve fibers showing TH-LI and NPY-LI, whereas the other peptide-containing nerve fibers remained unaffected. Vagotomy did not reduce the immunoreactivity for any of the neuropeptides studied. Capsaicin treatment caused a reduction in nerve fibers displaying SP-LI and CGRP-LI. The abundance of nerve fibers showing SP-LI and CGRP-LI in the keratinized squamous epithelium indicates that the tympanic membrane is richly supplied with sensory nerves. The localization of nerve fibers exhibiting these latter substances in the vicinity of mast cells in the pars flaccida suggests that this part of the tympanic membrane is a site where neurogenic inflammation occurs.

Animals↗

PubMed1989

Neuropeptide Y-like immunoreactivity in relation to the distribution of sympathetic nerve fibers in the heart conduction system.

The distribution of nerve fibers showing neuropeptide Y-like immunoreactivity (NPY-LI) was compared with the distribution of the sympathetic nerve fibers in all parts of the conduction system and adjacent atrial and ventricular tissue of the bovine heart. Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) served as markers for the sympathetic nerve fibers. NPY-LI was detected in most of the sympathetic nerve fibers that were present in nerve fascicles and that were associated with conduction cells and arterial walls in all regions examined. This phenomenon was more apparent when staining for NPY was compared with staining for DBH than with staining for TH. It was also found that some nerve varicosities exhibiting NPY-LI in association with arterial walls and local ganglia did not show DBH-LI. Furthermore, some of the ganglionic cells located in the regions of the conduction system showed NPY-LI but not DBH- or TH-LI. The observations are discussed in relation to what is known of the subcellular localization of NPY, TH and DBH. It is furthermore concluded that an NPY-like peptide is present in the sympathetic innervation of all parts of the conduction system and ordinary myocardial tissue, but that this peptide is also present in nerve fibers in the heart that do not represent sympathetic fibers. The observations raise important questions for further research aimed at determining the effects of NPY in relation to the function of the conduction system and in relation to the functions of not only sympathetic but also non-sympathetic nerve fibers in the heart.

Animals↗

PubMed1989

Establishment and functional implications of B-cell connectivity.

We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the organism; that the complementarities constituting this connectivity are based on self-self interactions, high degrees of degeneracy or somatically selected interactions and that these properties are conserved through evolution, to ensure self-reference; that by evolutionary selection, antibody V-genes encoding such structural properties are ensured to be expressed early in ontogeny. The set of highly connected cells will be kept through ontogeny and form the basis for a compartment of naturally-activated lymphocytes making up 10-15% of the total lymphocyte population. As suggested before, this pool of connected cells may be responsible for maintenance of normal network dynamics and prevention of autoaggression.

Amino Acid Sequence↗

PubMed1988

The distribution of terminal sympathetic nerve fibers in bundle branches and false tendons of the bovine heart. An immunohistochemical and catecholamine histofluorescence study.

The sympathetic innervation in false tendons as a whole and the distribution of the terminal sympathetic nerve fibers in the conduction tissue in the bundle branches is unclear. Therefore, in the present study, false tendons and bundle branch regions of the bovine heart were examined using tyrosine hydroxylase (TH) immunohistochemistry and the glyoxylic acid induced catecholamine (CA) fluorescence method for demonstration of sympathetic nerve fibers. Acetylcholinesterase (AChE) histochemistry was also applied. Some of the nerve fascicles in the false tendons were found to contain large numbers of sympathetic nerve fibers and such nerve fibers formed plexuses in the walls of arteries and arterioles in these structures. In both false tendons and bundle branches sympathetic nerve fibers 1) were non-homogeneously distributed in the conduction tissue, most regularly occurring in the channels of extracellular space that are present within the bundles of Purkinje fibres, and 2) showed the same pattern of distribution in relation to Purkinje fibre bundle surfaces as the AChE-positive nerve branches. The observations show that there is a substantial sympathetic innervation in false tendons. The final distribution of the nerve fibers in these structures and in the bundle branches are discussed in relation to what is known of tissue morphology and the occurrence of sympathetic nerve influences in these regions. In the present study, previous CA-fluorescence observations of a "marked" sympathetic innervation in bundle branch regions, in terms of the presence of sympathetic nerve fibers in nerve fascicles and vessel walls, were also corroborated by the application of TH-immunohistochemistry.

Animals↗