| 1. |
- Greiff, Lennart, et al.
(författare)
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Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
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| 2. |
- Korsgren, Magnus, et al.
(författare)
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Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice
- 1997
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Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 185:5, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins (Ig), particularly IgE, are believed to be crucially involved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous mutant C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 micrograms ovalbumin (OVA) plus alum, followed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus saline (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung and large airway tissues obtained 24 h after the last OVA or SAL exposure were examined by light microscopy and transmission electron microscopy (TEM). The Ig-deficient mice receiving OVA/ OVA treatment had swollen and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/ SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/unit area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL mice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Corresponding experiments in wild-type mice (n = 6-7 in each group) showed qualitatively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4+ T cells increased in lungs of all OVA/OVA-treated mice. Mast cell number did not differ but degranulation was detected only in OVA/OVA-treated wild-type mice. Immunization to OVA followed by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.
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| 3. |
- Persson, Carl, et al.
(författare)
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The mouse trap
- 1997
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Ingår i: Trends in Pharmacological Sciences. - 0165-6147. ; 18:12, s. 465-467
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Tidskriftsartikel (refereegranskat)abstract
- Mouse models of asthma are now being used extensively in drug research. However, the successful unravelling of combinatorial interplays of cells and molecules in the murine airways may not be matched by equally successful demonstrations of an asthma-like pathophysiology. Here, Carl Persson, Jonas Erjefalt, Magnus Korsgren and Frank Sundler discuss the fact that major features of asthma may still need to be demonstrated in the airways of allergic mice.
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| 4. |
- Ohlsson, Bodil, et al.
(författare)
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The method of administration of cholecystokinin determines the effects evoked in the pancreas
- 2001
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Ingår i: Pancreas. - 0885-3177. ; 23:1, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have shown different effects on cell proliferation and weight characteristics by sulfated cholecystokinin-8 (CCK-8S) in the rat pancreas when the peptide has been administered continuously rather than intermittently. The aim of this study was as follows: (i) to compare the effect of continuous infusion and of intermittent injections of CCK-8S on cell proliferation, weight gain, and induction of apoptosis and (ii) to examine the effect of injections of CCK-8S on CCK-A receptor gene expression in the rat pancreas. Male Sprague-Dawley rats had subcutaneous continuous infusion of CCK-8S in a dose of 5 microg/kg/h or 1% bovine serum albumin (BSA) (vehicle) by implanted osmotic minipumps. The rats were killed after 4 days. Other rats were either injected subcutaneously only once or injected twice daily for 3 days with either 6 microg of CCK dissolved in 0.5 mL BSA or 0.5 mL BSA alone. The rats were killed 1, 3, 6, and 12 hours after the last injection. One hour before death they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally to localize and quantitate the cell proliferation. Plasma was collected for analysis of CCK. The pancreas was dissected and immunohistochemistry was performed for analysis of the expression of the apoptosis promoting protein bax and the apoptosis inhibiting protein bcl-2, and for BrdU and CCK-A receptor localization. In situ hybridization (ISH) was used for examination and semiquantification of CCK-A receptor mRNA expression. Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight without any effect on BrdU labeling. Immunohistochemistry revealed decreased tissue expression of bax but unaffected expression of bcl-2. Intermittent injections of CCK-8S led to hyper-CCK-emia with increased incorporation of BrdU, indicating increased cell proliferation but no increase in pancreatic weight. Immunohistochemistry showed increased expression of bax, whereas bcl-2 remained unchanged. Immunofluorescence and ISH for the CCK-A receptor and its gene expression, respectively, showed a lowest intensity at 3 hours after CCK-8S injections. The results indicate that decreased apoptosis could explain the increased pancreatic weight during continuous infusion of CCK-8S. An increased apoptosis could explain the lack of pancreatic weight gain upon intermittent injections of CCK-8S despite the stimulation of cell proliferation. Injections of CCK-8S only transiently decreased the tissue levels of its receptor.
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| 5. |
- Uddman, Rolf, et al.
(författare)
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Neuropeptide-containing nerve fibers in the pharynx of the rabbit
- 1990
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Ingår i: Dysphagia. - 1432-0460. ; 4:4, s. 220-226
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle.
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| 6. |
- Karlsson, Sven, et al.
(författare)
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Beta cell adaptation to dexamethasone-induced insulin resistance in rats involves increased glucose responsiveness but not glucose effectiveness
- 2001
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Ingår i: Pancreas. - 0885-3177. ; 22:2, s. 148-156
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Tidskriftsartikel (refereegranskat)abstract
- Islet beta cell adaptation to dexamethasone-induced insulin resistance was characterized with respect to glucose-stimulated insulin secretion and islet innervation. Male Sprague-Dawley rats were injected daily with dexamethasone (2 mg/kg for 12 days), which resulted in hyperinsulinemia and hyperglycemia compared with controls (which were injected with sodium chloride). Insulin secretion was characterized in collagenase-isolated islets. Islet innervation was examined by immunocytochemical analysis of tyrosine hydroxylase, neuropeptide Y (sympathetic nerves), and vasoactive intestinal polypeptide (cholinergic nerves). In islets isolated from the insulin-resistant animals, the insulin response to 3.3 or 8.3 mM glucose was three times greater during perifusion compared with controls (p < 0.001). Incubation of islets at 0 to 20 mM glucose revealed a marked leftward shift of the glucose dose-response relation after dexamethasone treatment (potency ratio, 1.78; p < 0.01), with no difference at 0 or 20 mM glucose. Thus, the potency but not the efficacy of glucose was increased. The number of islet nerves did not differ between dexamethasone-treated rats and controls. Dexamethasone-induced insulin resistance leads to adaptively increased glucose responsiveness of the islet beta cells, with increased potency, but not increased efficacy, of glucose to stimulate insulin secretion without any evidence of altered islet innervation.
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| 7. |
- Järhult, Johannes, et al.
(författare)
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First Report on Metastasizing Small Bowel Carcinoids in First-Degree Relatives in Three Generations
- 2010
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 91:4, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: There is an established association between the multiple endocrine neoplasia type 1 (MEN 1) syndrome and foregut carcinoids. Some registry studies also indicate that offspring to carcinoid patients run an increased risk of developing a carcinoid tumor themselves. However, there are only scattered reports of gastrointestinal carcinoids in two generations. The aim of this study was to describe the clinical characteristics as well as the histopathological, immunohistochemical (IHC) and genetic data of metastasizing ileal carcinoids in three consecutive first-degree relatives. Methods: The histopathological and IHC analyses were performed on newly cut sections of the tumor specimens and included growth pattern, proliferation index (Ki67) as well as expression of established neuroendocrine markers and recently introduced cocaine-amphetamine-regulated transcript (CART). The genetic analyses were focused on establishing whether a connection with the MEN 1 syndrome existed in this family, by means of mutation screening using polymerase chain reaction, multiple ligation-dependent probe amplification, and genotyping using fluorescent-labeled microsatellite markers. Results: Histopathology and IHC revealed that the tumors were virtually identical, with only minor differences in proliferation index and expression of CART. Genetic analyses indicated that the inheritance of the small bowel carcinoids in the family was not linked to the MEN1 gene. Conclusion: Metastasizing small bowel carcinoids have been found in first-degree relatives in three consecutive generations. All three tumors were very similar when characterized by histopathology and IHC. Based on clinical findings and genetic analyses, it seems unlikely, although not completely excluded, that inheritance was linked to the MEN 1 syndrome. Copyright (c) 2010 S. Karger AG, Basel
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| 8. |
- Uddman, Rolf, et al.
(författare)
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Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2.
- 2002
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:2, s. 112-116
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Tidskriftsartikel (refereegranskat)abstract
- In migraine and other primary headaches there is a strong vascular component. Besides the trigeminovascular components some of the associated symptoms point to the involvement of brain stem regions. The central limb of the trigeminal vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and to the C1-C2 levels of the spinal cord. The aim of the present study was to demonstrate the occurrence of some neurotransmitters in these regions in man. In both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1 and C2 levels there were numerous substance P immunoreactive fibres. Fibres containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) were moderately dense in number. Fibres containing vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen in the TNC or at the C1 and C2 levels of the spinal cord.
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| 9. |
- Erjefält, Jonas, et al.
(författare)
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Microcirculation-derived factors in airway epithelial repair in vivo
- 1994
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 48:2, s. 161-178
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Tidskriftsartikel (refereegranskat)abstract
- Airway epithelial repair, by cell migration over a denuded, intact basement membrane, occurs rapidly in vivo. The present study examines microcirculation-derived factors in the reepithelialization process in the guinea pig. A well-defined tracheal zone was gently deepithelialized; no bleeding occurred and the basement membrane was left intact. Plasma exudation was visualized by use of iv colloidal gold (diameter: 5 nm) or fluoresceinisothiocyanate-labeled dextran. Scanning and transmission electron microscopy confirmed the migration of epithelial cells and, additionally, allowed us to examine the presence of an extracellular matrix gel and leukocytes on the denuded basement membrane. Fibronectin was analyzed by immunocytochemistry. Following epithelial removal plasma promptly extravasates and produces a fibrin-fibronectin gel to cover the denuded basement membrane. Epithelial cells dedifferentiate, flatten, and migrate rapidly (several micron/min) beneath the plasma-derived gel. Within 30 min the gel contains numerous leukocytes, some of which are eosinophils. Plasma exudes into the gel until about 8 hr by which time the entire denuded zone (800 microns) is covered by squamous epithelium. The fibrin-fibronectin gel is suggested to be exclusively plasma-derived. In conclusion, reepithelialization in vivo occurs beneath a gel containing adhesive plasma proteins and leukocytes. We suggest that a plasma exudate provides immediate cover of denuded airway basement membrane and that plasma- and leukocyte-derived factors contribute essentially to reepithelialization in vivo.
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| 10. |
- Ekblad, Eva, et al.
(författare)
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Innervation of the small intestine.
- 2002
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Ingår i: Biology of the Intestine in Growing Animals. - 9780444509284 - 0444509283 ; , s. 235-235
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Intestinal activities are controlled and co-ordinated by way of neuronal reflexes involving both extrinsic and intramural neurones, the enteric nervous system (ENS). This review focuses on the organisation, development and functional properties of the intestinal innervation and of the neurotransmitters utilised.
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