Rolf Uddman - Academia.edu (original) (raw)
Papers by Rolf Uddman
Digestive Diseases and Sciences, 1986
Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from... more Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polyptpeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neu-168 ropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.
Gastroenterology, 1983
Vasoactive intestinal polypeptide-containing nerves were examined in the lower esophagus of contr... more 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.
Digestion, 1987
The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens fr... more The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens from the human lower esophageal sphincter region by immunocytochemistry and immunochemistry. Normal individuals and patients suffering from achalasia or hiatus hernia with severe gastroesophageal reflux were examined. NPY fibers were found within and around smooth-muscle bundles of the longitudinal and the circular muscle layers and within the myenteric ganglia. Smooth-muscle specimens from patients with hiatus hernia and gastroesophageal reflux displayed numerous NPY fibers and an increased content of NPY. Specimens from patients with achalasia contained only few NPY fibers and had a decreased content of NPY as compared to specimens from control patients. Conceivably, NPY may play a role in the regulation of the lower esophageal sphincter.
Clinical & Experimental Allergy
Neuro endocrinology letters
Endothelin is a potent peptide mediator that is synthesized by a number of cells. Previous studie... more Endothelin is a potent peptide mediator that is synthesized by a number of cells. Previous studies have revealed the occurrence of endothelin in nerve cell bodies of some peripheral ganglia. Endothelin mediates its effects via two distinct receptor subtypes ETA and ETB. The present study was designed to investigate the presence of these two receptors in the human trigeminal ganglion. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to show the presence of mRNA encoding ETA and ETB receptors in the human trigeminal ganglion. To localize the protein immunocytochemistry with antibodies against the endothelin receptors was used. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed mRNA for both receptor subtypes in the human trigeminal ganglion. Immunocytochemistry revealed numerous cell bodies containing the ETA and the ETB receptor proteins. The expression of ETA and ETB receptors in the human trigeminal ganglion suggests a role for endothelin in autonomic and sensory neural transmission.
Neuro endocrinology letters
The purpose of this study was to localize in cranial ganglia of man the occurrence of the putativ... more The purpose of this study was to localize in cranial ganglia of man the occurrence of the putative gaseous neural messenger carbon monoxide (CO) and the biliverdin degrading enzyme biliverdin reductase (BVR). Immunocytochemistry with antibodies against the CO-inducing enzymes HO-1, HO-2, BVR and calcitonin gene-related peptide was used. In the trigeminal ganglion about 60% of the cell bodies exhibited HO-2- and about 40% BVR-immunoreactivity. HO-2- as well as BVR-immunoreactivity was predominantly (78%) expressed in medium-sized cells (30-60 microm). In the superior cervical ganglion about 40% of the cell bodies exhibited HO-2-immunoreactivity. In the sphenopalatine and otic ganglia only a few cell bodies were HO-2 immunoreactive. HO-1, the inducible isoform of heme oxygenase, gave only very weak immunoreactivity in all ganglia examined. Double immunostaining revealed that in the human trigeminal ganglion HO-2 and BVR co-localized with calcitonin gene-related peptide. The finding suggests that CO might serve as a modulator of synaptic transmission in man.
Investigative Ophthalmology & Visual Science
Neuropeptide Y (NPY) is a recently discovered, amidated 36 amino acid residue neuropeptide presen... more Neuropeptide Y (NPY) is a recently discovered, amidated 36 amino acid residue neuropeptide present in many but not all sympathetic noradrenergic neurons. In the guinea-pig eye, NPY immunoreactive fibers were found to have the same distribution as noradrenergic fibers except that there were fewer at the iris dilator, in the cornea, and in the chamber angle. In the anterior uvea, the NPY immunoreactive fibers disappeared after excision of the homolateral superior cervical sympathetic ganglion, whereas in the choroid, many NPY immunoreactive fibers remained, indicating that they originate elsewhere. NPY immunoreactivity thus is not found in all sympathetic adrenergic neurons nor is it found only in such nerve fibers. In the retina, NPY immunoreactive fibers formed a single layer of processes in sublamina 1 of the inner plexiform layer. NPY immunoreactive cell bodies were found in the innermost cell row of the inner nuclear layer. The immunoreactivity was concentrated to the hillock reg...
Albrecht von Graæes Archiv für Ophthalmologie
To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activati... more To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) in ocular and orbital structures of the cat. Immunocyto-chemistry to localize PACAP and double immunostaining to detect co-localization of PACAP with other neuropeptides. Numerous PACAP-immunoreactive nerve fibers were observed in the lacrimal gland, choroid and retroocular arteries. There was a sparse supply of PACAP-containing nerve fibers in the iris, ciliary body and conjunctiva. Subpopulations of PACAP-containing nerve fibers stored vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP). Around 10% of the ganglion cells in the sphenopalatine ganglion harbored PACAP immunoreactivity. In the trigeminal ganglion around 5% of the neuronal cell bodies and in the ciliary ganglion only occasional ganglion cells contained PACAP immunoreactivity. PACAP immunoreactivity co-localized with VIP in the sphenopalatine ganglion and with CGRP in the trigemin...
European Respiratory Journal
Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities ... more Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial se...
Respiratory research, 2007
Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocy... more Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis. The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively. TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid....
Respiratory research, 2005
Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular ... more Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors ...
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 1988
The neuropeptide vasoactive intestinal polypeptide (VIP), which is found in a population of choli... more The neuropeptide vasoactive intestinal polypeptide (VIP), which is found in a population of cholinergic parasympathetic neurons in the airways, has no effects per se on mucociliary activity. In order to test the hypothesis that VIP may modulate cholinergic regulation of the mucociliary system, VIP was infused intraarterially (8.4 pmol/kg/min), and the response to challenges with methacholine in the maxillary sinus of rabbits were recorded with a photoelectric technique. Occurrence of VIP-like immunoreactivity in the rabbit maxillary sinus, maxillary nerve, and sphenopalatine ganglion was investigated. Immunoreactivity against VIP was found in nerve fibers in the subepithelial layer of the maxillary sinus and in numerous nerve cell bodies in the sphenopalatine ganglion. Infusion of VIP potentiated the mucociliary increase induced by methacholine. The mucociliary wave frequency change increased from 6.1% +/- 1.7% to 13.3% +/- 3.9% (0.01 micrograms/kg methacholine), from 11.6% +/- 3.6%...
Neuroscience Letters, 1999
Noradrenaline (NA)-and neuropeptide Y (NPY)-containing cell bodies were found to occur in high nu... more Noradrenaline (NA)-and neuropeptide Y (NPY)-containing cell bodies were found to occur in high numbers (Ͼ75% of all cells were positive) in the human superior cervical ganglion and distributed homogeneously throughout the ganglion and showed colocalisation. A few cell bodies were VIP-immunoreactive (-ir) (less than 5%) but none of them showed NOS-, CGRP-or SP-ir. Receptor mRNA expression was studied with RT-PCR. Total RNA from the superior cervical ganglion was successfully extracted. By using appropriate sense and antisense oligonucleotides designed from the published human sequences, we could show the presence of mRNA for the human NPY Y 1 , NPY Y 2 and VPAC 1 receptors but not CGRP 1 receptor mRNA.
Respiratory Research, 2012
Background: S100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim... more Background: S100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim of the present study was to explore the expression and regulation of S100A7 in seasonal allergic rhinitis (SAR).
Regulatory Peptides, 1988
Nerve fibres displaying neurokinin A (NKA)-immunoreactivity (IR) were seen in trigeminal nerve ce... more Nerve fibres displaying neurokinin A (NKA)-immunoreactivity (IR) were seen in trigeminal nerve cell bodies and around cerebral blood vessels. NKA-positive fibres had the same general distribution as those displaying substance P (SP)-IR. Double or sequential immunostaining revealed coexistence of NKA-and SP-IR in a population of small nerve cell bodies in the trigeminal ganglion and in perivascular nerve fibres of brain vessels; both tachykinins were also noted to coexist with calcitonin gene-related peptide (CGRP)-IR. The presence of NKA-and SP-IR in cerebral vessels from guinea pig was verified by high-performance liquid chromatography and radioimmunochemistry. The levels NKA-IR were higher than those of SP-IR in cerebral vessels of rat, guinea pig and rabbit. In cat, pig, cow and human brain vessels, the levels of NKA-and SP-IR were equal. Major cerebral vessels at the base of the brain contained higher levels of NKA-and SP-IR than pial vessels on the cerebral convexities. Only low levels of NKA-IR and SP-IR were measured in choroid plexus and dura mater. Precontracted isolated arterial segments of middle cerebral (cat), basilar (rabbit, guinea pig and rat) and pial arteries (man) relaxed following the in vitro administration of NKA and SP. The responses occurred in the same concentration range; the IC5o value for NKA was, however, about 10 times higher than that for SP, while the maximum relaxation was equal. In basilar arteries from guinea pig, the peptides NKA, SP and CGRP all induced strong and potent relaxations. There was no evidence that one of the peptides might potentiate the relaxant effects in vitro of another. The present data suggest that NKA, SP and CGRP are costored and can be released together and cooperate in the mediation of vascular reactions in response to activation of the trigemino-cerebrovascular pathway.
Regulatory Peptides, 1991
The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclas... more The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclase activating peptide (PACAP), a novel vasoactive intestinal peptide (VIP)-like peptide, using immunocytochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were numerous in the longitudinal and circular muscle layers of sheep and man, moderate in numbers in cat, while being few in the esophagus of guinea-pig. A few PACAP-immunoreactive nerve cell bodies and numerous nerve fibers were seen in the myenteric ganglia of the esophagus of cat, sheep and man. In the lower esophagus of cat, sheep and man all PACAP-containing nerve cell bodies and nerve fibers stored VIP. The results of radioimmunoassay of PACAP in extracts of specimens from man were in good agreement with the immunocytochemical findings. High performance liquid chromatography revealed one major peak of PACAP-like immunoreactivity in extracts of human esophagus. We suggest that neuronal PACAP may serve to modulate motor activity and secretion in the lower esophageal sphincter region.
Pulmonary Pharmacology & Therapeutics, 2008
Cytokines like interleukin-1b (IL-1b) and tumor necrosis factor a (TNFa), released during the inf... more Cytokines like interleukin-1b (IL-1b) and tumor necrosis factor a (TNFa), released during the inflammatory process, play important roles in the development of airway hyperresponsiveness. The effects of these cytokines are mediated by cell surface receptors, specific for each cytokine. The expression of cytokine receptors is a dynamic process, where receptors can be up-or down-regulated in response to changes in the environment. One such environmental factor is the presence of cytokines per se. The present study was designed to evaluate the effects of IL-1b on the expression of its corresponding receptor IL-1 RI, as well as on the closely related TNFa receptors TNF RI and TNF RII in airways using a mouse organ culture assay and intranasal inoculation model. Immunohistochemical staining was used to quantify expressional differences between fresh and cultured tracheal segments. In the fresh, uncultured, segments, IL-1 RI and TNF RI were seen in the epithelial layer and TNF RI in the smooth muscle layer. After 4 days of culture, the expression of TNF RI decreased in the epithelial layer, whereas the corresponding expression of IL-1 RI and TNF RI in the smooth muscle remained unchanged. When culture was performed in the presence of IL-1b, the expression of IL-1 RI and TNF RI in the epithelial cells and TNF RI in the smooth muscle cells increased. TNF RII was not detected in either fresh or cultured trachea, but after treatment with IL-1b an expression was found in both the epithelial layer and in the smooth muscle cells. The IL-1b-induced increased expression, on TNF RI and TNF RII in the smooth muscle ex vivo and in the lung parenchyma after intranasal challenge in vivo, was verified at the mRNA level using real-time RT PCR. To summarize, presence of IL-1b increases the expression of IL-1 R1 and TNF RI and induces expression of TNF RII in the airway wall. It is not inconceivable that these alterations of the IL-1 and TNF receptors may have important functional implications for the development of hyperresponsiveness in inflammatory airway diseases like asthma.
Proceedings of the National Academy of Sciences, 1983
The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rat... more The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rats to investigate the functional consequences (reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of vasoactive intestinal polypeptide. Intrastriatal administration of vasoactive intestinal polypeptide (20 pmol) significantly increased local glucose utilization in the injected striatum, where the increased use was localized in small punctate areas (100-500 microns wide in coronal sections) scattered throughout the nucleus at considerable distances (up to 4 mm) from the injection site. Significantly increased glucose utilization after intrastriatal injection of vasoactive intestinal polypeptide was observed in a number of regions (e.g., substantia nigra pars compacta, entopeduncular nucleus, lateral habenular nucleus, entorhinal, pyriform cortices, and amygdala) with known primary or secondary neuronal connections with the caudate nucleus. These alterations in glucose utilization were highly focal in nature, with the majority (40 of the 50 examined) of brain regions displaying unaltered rates of glucose utilization. The data provide evidence, obtained in conscious animals, that vasoactive intestinal polypeptide can modify functional processes in the caudate nucleus.
PLoS ONE, 2012
Head and neck squamous cell carcinoma (HNSCC) is known to cause substantial immunosuppression. Th... more Head and neck squamous cell carcinoma (HNSCC) is known to cause substantial immunosuppression. The present study was designed to characterize blood leukocyte activation in HNSCC and to investigate if the individual activation pattern could be related to tumor progress and survival. The leukocyte activation profile of HNSCC patients and healthy controls was assessed with flow cytometry. HNSCC patients displayed increased numbers of monocytes, neutrophils and total leukocytes as well as an enhanced neutrophil/lymphocyte ratio. In addition, patients had a higher percentage of CD69 + , CD71 + and CD98 + T cell subsets and NK cells, and a reduced expression of L-selectin in CD14 high CD16 + monocytes and neutrophils, when compared to controls. These changes could be correlated to both tumor burden and spread to lymph nodes. Among the cancer patients an increased neutrophil/lymphocyte ratio, a low neutrophil and CD14 high CD16 + monocyte activation state and an elevated CD4/CD8 ratio were related to poor survival. In contrast, a high percentage of CD98 + Th cells appeared to be associated with a better outcome. Taken together, the present data indicate that HNSCC causes activation of blood leukocytes and that the individual activation pattern can be linked to prognosis.
Digestive Diseases and Sciences, 1986
Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from... more Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polyptpeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neu-168 ropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.
Gastroenterology, 1983
Vasoactive intestinal polypeptide-containing nerves were examined in the lower esophagus of contr... more 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.
Digestion, 1987
The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens fr... more The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens from the human lower esophageal sphincter region by immunocytochemistry and immunochemistry. Normal individuals and patients suffering from achalasia or hiatus hernia with severe gastroesophageal reflux were examined. NPY fibers were found within and around smooth-muscle bundles of the longitudinal and the circular muscle layers and within the myenteric ganglia. Smooth-muscle specimens from patients with hiatus hernia and gastroesophageal reflux displayed numerous NPY fibers and an increased content of NPY. Specimens from patients with achalasia contained only few NPY fibers and had a decreased content of NPY as compared to specimens from control patients. Conceivably, NPY may play a role in the regulation of the lower esophageal sphincter.
Clinical & Experimental Allergy
Neuro endocrinology letters
Endothelin is a potent peptide mediator that is synthesized by a number of cells. Previous studie... more Endothelin is a potent peptide mediator that is synthesized by a number of cells. Previous studies have revealed the occurrence of endothelin in nerve cell bodies of some peripheral ganglia. Endothelin mediates its effects via two distinct receptor subtypes ETA and ETB. The present study was designed to investigate the presence of these two receptors in the human trigeminal ganglion. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to show the presence of mRNA encoding ETA and ETB receptors in the human trigeminal ganglion. To localize the protein immunocytochemistry with antibodies against the endothelin receptors was used. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed mRNA for both receptor subtypes in the human trigeminal ganglion. Immunocytochemistry revealed numerous cell bodies containing the ETA and the ETB receptor proteins. The expression of ETA and ETB receptors in the human trigeminal ganglion suggests a role for endothelin in autonomic and sensory neural transmission.
Neuro endocrinology letters
The purpose of this study was to localize in cranial ganglia of man the occurrence of the putativ... more The purpose of this study was to localize in cranial ganglia of man the occurrence of the putative gaseous neural messenger carbon monoxide (CO) and the biliverdin degrading enzyme biliverdin reductase (BVR). Immunocytochemistry with antibodies against the CO-inducing enzymes HO-1, HO-2, BVR and calcitonin gene-related peptide was used. In the trigeminal ganglion about 60% of the cell bodies exhibited HO-2- and about 40% BVR-immunoreactivity. HO-2- as well as BVR-immunoreactivity was predominantly (78%) expressed in medium-sized cells (30-60 microm). In the superior cervical ganglion about 40% of the cell bodies exhibited HO-2-immunoreactivity. In the sphenopalatine and otic ganglia only a few cell bodies were HO-2 immunoreactive. HO-1, the inducible isoform of heme oxygenase, gave only very weak immunoreactivity in all ganglia examined. Double immunostaining revealed that in the human trigeminal ganglion HO-2 and BVR co-localized with calcitonin gene-related peptide. The finding suggests that CO might serve as a modulator of synaptic transmission in man.
Investigative Ophthalmology & Visual Science
Neuropeptide Y (NPY) is a recently discovered, amidated 36 amino acid residue neuropeptide presen... more Neuropeptide Y (NPY) is a recently discovered, amidated 36 amino acid residue neuropeptide present in many but not all sympathetic noradrenergic neurons. In the guinea-pig eye, NPY immunoreactive fibers were found to have the same distribution as noradrenergic fibers except that there were fewer at the iris dilator, in the cornea, and in the chamber angle. In the anterior uvea, the NPY immunoreactive fibers disappeared after excision of the homolateral superior cervical sympathetic ganglion, whereas in the choroid, many NPY immunoreactive fibers remained, indicating that they originate elsewhere. NPY immunoreactivity thus is not found in all sympathetic adrenergic neurons nor is it found only in such nerve fibers. In the retina, NPY immunoreactive fibers formed a single layer of processes in sublamina 1 of the inner plexiform layer. NPY immunoreactive cell bodies were found in the innermost cell row of the inner nuclear layer. The immunoreactivity was concentrated to the hillock reg...
Albrecht von Graæes Archiv für Ophthalmologie
To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activati... more To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) in ocular and orbital structures of the cat. Immunocyto-chemistry to localize PACAP and double immunostaining to detect co-localization of PACAP with other neuropeptides. Numerous PACAP-immunoreactive nerve fibers were observed in the lacrimal gland, choroid and retroocular arteries. There was a sparse supply of PACAP-containing nerve fibers in the iris, ciliary body and conjunctiva. Subpopulations of PACAP-containing nerve fibers stored vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP). Around 10% of the ganglion cells in the sphenopalatine ganglion harbored PACAP immunoreactivity. In the trigeminal ganglion around 5% of the neuronal cell bodies and in the ciliary ganglion only occasional ganglion cells contained PACAP immunoreactivity. PACAP immunoreactivity co-localized with VIP in the sphenopalatine ganglion and with CGRP in the trigemin...
European Respiratory Journal
Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities ... more Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial se...
Respiratory research, 2007
Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocy... more Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis. The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively. TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid....
Respiratory research, 2005
Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular ... more Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors ...
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 1988
The neuropeptide vasoactive intestinal polypeptide (VIP), which is found in a population of choli... more The neuropeptide vasoactive intestinal polypeptide (VIP), which is found in a population of cholinergic parasympathetic neurons in the airways, has no effects per se on mucociliary activity. In order to test the hypothesis that VIP may modulate cholinergic regulation of the mucociliary system, VIP was infused intraarterially (8.4 pmol/kg/min), and the response to challenges with methacholine in the maxillary sinus of rabbits were recorded with a photoelectric technique. Occurrence of VIP-like immunoreactivity in the rabbit maxillary sinus, maxillary nerve, and sphenopalatine ganglion was investigated. Immunoreactivity against VIP was found in nerve fibers in the subepithelial layer of the maxillary sinus and in numerous nerve cell bodies in the sphenopalatine ganglion. Infusion of VIP potentiated the mucociliary increase induced by methacholine. The mucociliary wave frequency change increased from 6.1% +/- 1.7% to 13.3% +/- 3.9% (0.01 micrograms/kg methacholine), from 11.6% +/- 3.6%...
Neuroscience Letters, 1999
Noradrenaline (NA)-and neuropeptide Y (NPY)-containing cell bodies were found to occur in high nu... more Noradrenaline (NA)-and neuropeptide Y (NPY)-containing cell bodies were found to occur in high numbers (Ͼ75% of all cells were positive) in the human superior cervical ganglion and distributed homogeneously throughout the ganglion and showed colocalisation. A few cell bodies were VIP-immunoreactive (-ir) (less than 5%) but none of them showed NOS-, CGRP-or SP-ir. Receptor mRNA expression was studied with RT-PCR. Total RNA from the superior cervical ganglion was successfully extracted. By using appropriate sense and antisense oligonucleotides designed from the published human sequences, we could show the presence of mRNA for the human NPY Y 1 , NPY Y 2 and VPAC 1 receptors but not CGRP 1 receptor mRNA.
Respiratory Research, 2012
Background: S100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim... more Background: S100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim of the present study was to explore the expression and regulation of S100A7 in seasonal allergic rhinitis (SAR).
Regulatory Peptides, 1988
Nerve fibres displaying neurokinin A (NKA)-immunoreactivity (IR) were seen in trigeminal nerve ce... more Nerve fibres displaying neurokinin A (NKA)-immunoreactivity (IR) were seen in trigeminal nerve cell bodies and around cerebral blood vessels. NKA-positive fibres had the same general distribution as those displaying substance P (SP)-IR. Double or sequential immunostaining revealed coexistence of NKA-and SP-IR in a population of small nerve cell bodies in the trigeminal ganglion and in perivascular nerve fibres of brain vessels; both tachykinins were also noted to coexist with calcitonin gene-related peptide (CGRP)-IR. The presence of NKA-and SP-IR in cerebral vessels from guinea pig was verified by high-performance liquid chromatography and radioimmunochemistry. The levels NKA-IR were higher than those of SP-IR in cerebral vessels of rat, guinea pig and rabbit. In cat, pig, cow and human brain vessels, the levels of NKA-and SP-IR were equal. Major cerebral vessels at the base of the brain contained higher levels of NKA-and SP-IR than pial vessels on the cerebral convexities. Only low levels of NKA-IR and SP-IR were measured in choroid plexus and dura mater. Precontracted isolated arterial segments of middle cerebral (cat), basilar (rabbit, guinea pig and rat) and pial arteries (man) relaxed following the in vitro administration of NKA and SP. The responses occurred in the same concentration range; the IC5o value for NKA was, however, about 10 times higher than that for SP, while the maximum relaxation was equal. In basilar arteries from guinea pig, the peptides NKA, SP and CGRP all induced strong and potent relaxations. There was no evidence that one of the peptides might potentiate the relaxant effects in vitro of another. The present data suggest that NKA, SP and CGRP are costored and can be released together and cooperate in the mediation of vascular reactions in response to activation of the trigemino-cerebrovascular pathway.
Regulatory Peptides, 1991
The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclas... more The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclase activating peptide (PACAP), a novel vasoactive intestinal peptide (VIP)-like peptide, using immunocytochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were numerous in the longitudinal and circular muscle layers of sheep and man, moderate in numbers in cat, while being few in the esophagus of guinea-pig. A few PACAP-immunoreactive nerve cell bodies and numerous nerve fibers were seen in the myenteric ganglia of the esophagus of cat, sheep and man. In the lower esophagus of cat, sheep and man all PACAP-containing nerve cell bodies and nerve fibers stored VIP. The results of radioimmunoassay of PACAP in extracts of specimens from man were in good agreement with the immunocytochemical findings. High performance liquid chromatography revealed one major peak of PACAP-like immunoreactivity in extracts of human esophagus. We suggest that neuronal PACAP may serve to modulate motor activity and secretion in the lower esophageal sphincter region.
Pulmonary Pharmacology & Therapeutics, 2008
Cytokines like interleukin-1b (IL-1b) and tumor necrosis factor a (TNFa), released during the inf... more Cytokines like interleukin-1b (IL-1b) and tumor necrosis factor a (TNFa), released during the inflammatory process, play important roles in the development of airway hyperresponsiveness. The effects of these cytokines are mediated by cell surface receptors, specific for each cytokine. The expression of cytokine receptors is a dynamic process, where receptors can be up-or down-regulated in response to changes in the environment. One such environmental factor is the presence of cytokines per se. The present study was designed to evaluate the effects of IL-1b on the expression of its corresponding receptor IL-1 RI, as well as on the closely related TNFa receptors TNF RI and TNF RII in airways using a mouse organ culture assay and intranasal inoculation model. Immunohistochemical staining was used to quantify expressional differences between fresh and cultured tracheal segments. In the fresh, uncultured, segments, IL-1 RI and TNF RI were seen in the epithelial layer and TNF RI in the smooth muscle layer. After 4 days of culture, the expression of TNF RI decreased in the epithelial layer, whereas the corresponding expression of IL-1 RI and TNF RI in the smooth muscle remained unchanged. When culture was performed in the presence of IL-1b, the expression of IL-1 RI and TNF RI in the epithelial cells and TNF RI in the smooth muscle cells increased. TNF RII was not detected in either fresh or cultured trachea, but after treatment with IL-1b an expression was found in both the epithelial layer and in the smooth muscle cells. The IL-1b-induced increased expression, on TNF RI and TNF RII in the smooth muscle ex vivo and in the lung parenchyma after intranasal challenge in vivo, was verified at the mRNA level using real-time RT PCR. To summarize, presence of IL-1b increases the expression of IL-1 R1 and TNF RI and induces expression of TNF RII in the airway wall. It is not inconceivable that these alterations of the IL-1 and TNF receptors may have important functional implications for the development of hyperresponsiveness in inflammatory airway diseases like asthma.
Proceedings of the National Academy of Sciences, 1983
The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rat... more The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rats to investigate the functional consequences (reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of vasoactive intestinal polypeptide. Intrastriatal administration of vasoactive intestinal polypeptide (20 pmol) significantly increased local glucose utilization in the injected striatum, where the increased use was localized in small punctate areas (100-500 microns wide in coronal sections) scattered throughout the nucleus at considerable distances (up to 4 mm) from the injection site. Significantly increased glucose utilization after intrastriatal injection of vasoactive intestinal polypeptide was observed in a number of regions (e.g., substantia nigra pars compacta, entopeduncular nucleus, lateral habenular nucleus, entorhinal, pyriform cortices, and amygdala) with known primary or secondary neuronal connections with the caudate nucleus. These alterations in glucose utilization were highly focal in nature, with the majority (40 of the 50 examined) of brain regions displaying unaltered rates of glucose utilization. The data provide evidence, obtained in conscious animals, that vasoactive intestinal polypeptide can modify functional processes in the caudate nucleus.
PLoS ONE, 2012
Head and neck squamous cell carcinoma (HNSCC) is known to cause substantial immunosuppression. Th... more Head and neck squamous cell carcinoma (HNSCC) is known to cause substantial immunosuppression. The present study was designed to characterize blood leukocyte activation in HNSCC and to investigate if the individual activation pattern could be related to tumor progress and survival. The leukocyte activation profile of HNSCC patients and healthy controls was assessed with flow cytometry. HNSCC patients displayed increased numbers of monocytes, neutrophils and total leukocytes as well as an enhanced neutrophil/lymphocyte ratio. In addition, patients had a higher percentage of CD69 + , CD71 + and CD98 + T cell subsets and NK cells, and a reduced expression of L-selectin in CD14 high CD16 + monocytes and neutrophils, when compared to controls. These changes could be correlated to both tumor burden and spread to lymph nodes. Among the cancer patients an increased neutrophil/lymphocyte ratio, a low neutrophil and CD14 high CD16 + monocyte activation state and an elevated CD4/CD8 ratio were related to poor survival. In contrast, a high percentage of CD98 + Th cells appeared to be associated with a better outcome. Taken together, the present data indicate that HNSCC causes activation of blood leukocytes and that the individual activation pattern can be linked to prognosis.