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Biomedical subjects

T Lyberg

Publications and source records attributed to T Lyberg.

At least 19 recordsLinked to original sources

Heterogeneity of procoagulant activity and cytokine release in subpopulations of alveolar macrophages and monocytes.

We have studied the expression of tissue factor (TF) and fibrinopeptide A (FPA) generation as well as the release capacity of TNF-alpha, IL-1beta, and IL-6 in density-defined subpopulations of alveolar macrophages (AM) and monocytes (Mo). TF was equally expressed on all AM subpopulations and Mo, while the FPA-forming capacity was at the same level in low density AM as in Mo and was significantly (P < 0.05) higher in low density AM than in high density AM. The lipopolysaccharide (LPS)-induced release of TNF-alpha was higher (P < 0.05) in high density AM than in low density AM and in Mo. IL-1beta release was undetectable in unstimulated AM and in LPS-stimulated low density AM, while the LPS-induced IL-1beta release in high density AM was low compared to the levels demonstrated in Mo. LPS-stimulated IL-6 release was not distinctively different in the AM subpopulations and Mo. The presented study showed that FPA generation and LPS-stimulated TNF-alpha release were dependent on the density (i.e., maturity) of AM. This implies that a skewed distribution of AM subpopulations induced by disease processes may profoundly influence the inflammatory reactions, including extravascular activation of coagulation.

Adult

Severe craniofacial malformations and deglutition dysfunction in a brother and sister: new syndrome?

We report seemingly unique craniofacial malformations and deglutition dysfunction in a sib pair. The boy had right maxillomandibular alveolar synechae, ankylosis of right temporomandibular joint, hypoplasia of the zygomatico-maxillary region, nasal deviation to the left, choanal stenosis, and exophthalmos due to shallow orbita. His ears were apparently low-set with prominent lobules. He had severe gastroesophageal reflux and increasing respiratory problems and died at age 11 months. Psychomotor development was normal. His 10-year-old sister had similar craniofacial malformations and a cleft soft palate. She also had a severe deglutition dysfunction and developed a thoracolumbar kyphoscoliosis. Psychomotor development was normal. The parents were healthy and non-consanguineous. The malformations in the sibs do not fit any reported craniofacial malformation syndrome and may represent a previously unrecognized monogenic disorder. This may be an autosomal recessive or dominant trait with gonadal mosaicism in one of the parents.

Abnormalities, Multiple

CD14 expression and binding of lipopolysaccharide to alveolar macrophages and monocytes.

We have studied the expression of the lipopolysaccharide (LPS) receptor CD14 on monocytes (Mo) and alveolar macrophages (AM), including density- and size-defined subpopulations. Bronchoalveolar lavage (BAL) was performed on eleven healthy non-smokers and blood sampled from 5 of them, and the levels of cell CD14 expression was investigated using flow cytometry. The influence of LPS stimulation on the CD14 expression of AM was studied at various intervals during prolonged incubation. Further, the relationship between CD14 expression and LPS binding to Mo and subpopulations of AM was studied by measuring fluorescein isothiocyanate (FITC)-LPS binding (flow cytometry) and binding of radioiodinated LPS (125I-LPS). The CD14 expression was 13-fold higher (P < 0.02) on Mo than on unfractionated and high density AM. The CD14 level on the latter was higher than on low density AM, and also higher (P < 0.05) on small AM compared to large (flow cytometrically defined) AM. LPS stimulation had a downregulating effect on AM CD14 level, but after several hours of continuing decreased expression, an increased (P < 0.05) CD14 expression was demonstrated, indicating de novo synthesis. The binding of LPS to subpopulations of AM and isolated Mo was not significantly different, but the binding of FITC-LPS to Mo in whole blood was higher than to AM (P < 0.02). The presented results indicate that AM of different size and maturity have different and variable (activation dependent) CD14 levels. The LPS binding capacity was, however, not proportional to the CD14 expression, indicating that LPS binding mechanisms unrelated to CD14 levels were also operable.

Adult

Large intravenous bilirubin loads increase the cytotoxicity of bile and lower the resistance of the canalicular membrane to cytotoxic injury and cause cholestasis in pigs.

BACKGROUND: Large intravenous bilirubin loads cause loss of hepatic canalicular membrane microvilli and cholestasis. This study examines whether these untoward effects might be due to canalicular membrane injury from cytotoxic bile. METHODS: The cytotoxicity of bile was assayed against pig erythrocytes before and throughout 4.5-h intravenous infusion of 170 microg kg(-1) body weight of bilirubin in anaesthetized pigs. The capacity to generate canalicular bile flow was tested before and after bilirubin infusion by means of short-term intraportal cholic acid infusion. RESULTS: Bilirubin infusion increased the cytotoxicity of hepatic bile, reduced biliary phospholipid secretion by 90%, and caused cholestasis. Cholic acid infusion before bilirubin also increased the cytotoxicity of bile but increased bile flow and doubled biliary phospholipid output. CONCLUSION: Large intravenous bilirubin infusions increase the cytotoxicity of bile, suppress biliary phospholipid secretion, and render hepatic canalicular membrane microvilli susceptible to injury from cytotoxic bile so that cholestasis occurs.

Animals

Increased synthesis and release of endothelin-1 during the initial phase of airway inflammation.

Recently, we have shown a substantial increase in the endothelin-1 (ET-1) concentration in bronchoalveolar fluid (BALF) during an experimental eosinophilic airway inflammation. Moreover, we observed a significant inhibition of the inflammatory response after treatment with an endothelin receptor antagonist. This indicates that ET-1 may have proinflammatory properties and play a key role in eosinophilic inflammations, such as bronchial asthma. Accordingly, we hypothesized that the synthesis and release of ET-1 precedes the inflammatory response, and that the bronchial epithelium is the site of ET-1 synthesis in the lungs. An eosinophilic airway inflammation was induced by intratracheal Sephadex instillation in rats, and the animals were evaluated after 15 min, 30 min, 1, 2, 3, 6, 12, and 48 h. The ET-1 mRNA synthesis, assessed by Northern and slot blot analyses, was significantly increased 15 min after Sephadex challenge, peaking at 30 min with a 4.7-fold increase, before any signs of inflammation in the BALF could be observed. The increased synthesis was mainly located to the bronchial epithelium and macrophages at sites of inflammation as determined by in situ hybridization. A significant increase in tissue ET-1 was observed 3 h after provocation, and the recruitment of eosinophils followed a substantial release of ET-1 peptide in BALF peaking at 24 h with a 13-fold increase. Therefore, the rapid ET-1 mRNA synthesis and the considerable increase in the level of ET-1 indicate that this peptide plays an important role in the initiation of an eosinophilic airway inflammation.

Animals

Expression of leukocyte integrins and tissue factor in mononuclear phagocytes.

Coagulation is intimately involved in the pathology of inflammation. The leukocyte beta2-integrins have several functions, including serving as receptors for coagulation factor X and fibrinogen. Tissue factor (TF) is a receptor for factor VII and a very potent trigger of coagulation. The intention of this study was to examine a possible coexpression of beta2-integrins (CD11b/CD18 and CD11c/CD18) and the procoagulant TF in alveolar macrophages (AM) and blood monocytes, i.e. cells of the same differentiation lineage. The expression of beta2-integrins in human AM isolated by bronchoalveolar lavage and in blood monocytes was analysed by flow cytometry, whereas TF activity was analysed in a one-stage clotting assay. In monocytes, TF activity, CD11b and CD11c expression were highly inducible by lipopolysaccharide (LPS), with a 13-, 19- and four-fold increase, respectively. In AM, TF and beta2-integrins were all constitutively expressed, but the expression could not be further enhanced by LPS stimulation. CD11b and CD11c expression varied inversely with the cell size of AM, in contrast to TF activity which is known to be proportional to AM cell size. In vitro expression of beta2-integrins and tissue factor in lipopolysaccharide-stimulated blood monocytes seems to be intimately coregulated, whereas the expression of these receptors in alveolar macrophages seems to be unresponsive to lipopolysaccharide. These results indicate that blood monocytes and alveolar macrophages have different roles and use different mechanisms in cell-induced fibrin formation.

Adult

Adhesion of leukocytes to growing arterial thrombi.

Since the role of leukocytes found present in thrombi and haemostatic plugs is not clearly understood. we have investigated the interaction between leukocytes and growing thrombi in a human ex vivo model of arterial thrombogenesis. At a wall shear rate characteristic of moderately stenosed arteries (2600 s(-1)), granulocytes selectively accumulated at the luminal surface of platelet thrombi. The leukocyte adhesion seemed independent of fibrin formation and was clearly correlated to thrombus growth and platelet activation. In contrast, flow cytometry revealed that the expression of adhesion molecules (CD11a, CD11b, CD11, CD3, CD14, CD62L, HLA-DR and binding of fibrinogen) on the surface of circulating leukocytes passing the thrombi was, on short term conditions (15 min), independent of thrombus growth. The adhered granulocytes probably play a pivotal role in limiting the size of the evolving thrombi, as suggested by our electron micrographs of the arterial thrombi showing lysed and phagocytosed platelets. Thus, granulocytes might play an active role in the acute/semiacute phase of local thromboregulation.

Adult

[Treatment of facial gunshot injuries].

Patients with gunshot injuries in the maxillofacial region should be resuscitated and subjected to a general examination in the emergency room. Chest X-rays and head CT scans should be performed on a routine basis, and in selected cases angiography and plain X-ray films of the cervical columns are also recommended. Treatment of the facial defects depends to some degree on the type of firearm involved, i.e. high velocity rifle, low velocity weapon or shotgun. The traditional treatment for war and civilian gunshot injuries to the face has been debridement, soft tissue closure and conservative treatment of fractures, with closed reduction and external fixation. This treatment may leave inadequate stabilization of remaining bone fragments, with collapse and later contraction of soft tissue. It fails to take advantage of the modern craniofacial and microsurgical techniques used in a more recent approach that can be termed initial final treatment of gunshot wounds. This treatment modality is recommended for civilian low velocity gunshot injuries and, after repeated debridements, also for injuries caused by shotguns and high velocity weapons.

Emergencies

Internal derangement of the temporomandibular joint: correlation of arthrographic imaging with surgical findings.

Sixty-seven patients, who were surgically treated for internal derangement of the temporomandibular joint (TMJ), were retrospectively examined. The patients were evaluated preoperatively by clinical and arthrographic examinations and these results were compared with findings at surgery. Partial or complete dislocation of the disc was detected by arthrographic examination in 65 joints. Actual disc displacement was demonstrated at surgery in 57 TMJs, giving arthrography a positive predictive value of 88% for detecting disc dislocation. Arthrographic diagnosis of disc perforation was unreliable, as both false positive and false negative observations were recorded. Arthrography was found to have a positive predictive value of only 53% for assessing disc perforation. Based upon its proven inaccuracy, invasiveness and discomfort to the patient, it is recommended to replace arthrography by magnetic resonance imaging.

Adult

Platelet activation in flowing blood passing growing arterial thrombi.

We investigated the combined effect of wall shear rate and immobilized collagen on platelet activation in flowing nonanticoagulated human blood. By combining an ex vivo model of thrombogenesis with flow cytometry, we showed that activated platelets can be detected in the bloodstream passing growing thrombi at a wall shear rate characteristic of moderately stenosed arteries (2600 s-1). The activation of the circulating platelets was clearly correlated with thrombus growth. Different antibodies against platelet activation-dependent surface markers had distinct sensitivity to the thrombotic process. alpha-Granule release detected by surface expression of CD62P seemed to be the most sensitive marker, as judged by both mean fluorescence intensity and fraction of platelets activated. The conformational change in glycoprotein IIb-IIIa, as detected by PAC-1, also seemed to be a sensitive marker and preceded binding of fibrinogen to activated glycoprotein IIb-IIIa, as detected by anti-fibrinogen. Large thrombi also elicited lysosome exocytosis, detected by surface expression of CD63. Finally, we observed a small decrease of glycoprotein Ib-IX expression, as detected by anti-CD42a. Thus, our study provides further information on the dynamics of platelet activation in relation to thrombus growth at arterial shear conditions in flowing nonanticoagulated human blood.

Adult

Endothelin production and effects of endothelin antagonism during experimental airway inflammation.

Endothelin (ET) has strong bronchoconstrictor properties, stimulate mucus secretion and mucosal edema, and may also exert proinflammatory effects. Therefore, ET may play a pathogenic role in inflammatory airway diseases such as bronchial asthma. The production and localization of ET and the effect of blocking ET receptors was investigated in rats during airway inflammation induced by intratracheal instillation of dextran (Sephadex). We observed a considerable increase in the concentration of ET in bronchoalveolar lavage fluid (BALF) during the early phase of inflammation, with an increase from 2.2 +/- 0.6 pg/ml in controls to 40.0 +/- 6.7 pg/ml at Day 1, declining to 5.3 +/- 1.1 pg/ml at Day 14. Correlated with the ET response in BALF was a considerable increase in total cell count (r = 0.61), eosinophils (r = 0.83), and neutrophils (r = 0.81). Plasma ET was not elevated. Immunohistochemical analyses revealed ET-like staining in the bronchial epithelium. Treatment with the ET receptor antagonist bosentan inhibited the increase in eosinophils in BALF and reduced the inflammatory reaction in the lung tissue. In summary, a considerable increase in the ET concentration in BALF was demonstrated during the acute phase of an experimental eosinophilic airway inflammation, coinciding with an increased ET-like immunostaining in the bronchial epithelium. Treatment with an ET receptor antagonist inhibited the inflammatory response in BALF and in the tissue.

Animals

Effects of heparin coating on the expression of CD11b, CD11c and CD62L by leucocytes in extracorporeal circulation in vitro.

Leucocyte adhesion molecules are involved in the leucocyte-endothelial interaction and in the activation of coagulation and binding of complement and endotoxin. Thus, they are important in inflammation, systemic acute phase reaction, ischaemia reperfusion injury and resistance against infections. The expression of the adhesion molecules CD11b, CD11c and CD62L on leucocytes and changes in plasma products of neutrophil activation (myeloperoxidase, lactoferrin) and complement activation (C3bc, SC5b-9 (TCC)) were examined in an extracorporeal circulation (ECC) model and the effects of Carmeda bioactive surface (CBAS) heparin coating (n = 7) of the circuits were compared to uncoated control circuits (n = 5). In this model, new 'unactivated' cells mobilized from the bone marrow could not interfere with descriptive measures of cell activation as seen in in vivo studies. In the control group, CD11b and CD11c were upregulated on monocytes and granulocytes during ECC, whereas CD62L was downregulated. Heparin coating reduced the increase in CD11b and CD11c on granulocytes (p < 0.02 at 2 h), but the delayed increase in CD11c on monocytes and the delayed downregulation of CD62L on granulocytes and monocytes did not reach statistical significance. Further, heparin coating also reduced the initial decrease in the absolute cell counts of monocytes and granulocytes (p = 0.01 at 2 h), reflecting reduced adhesion to the oxygenator/tubing. The increases in plasma myeloperoxidase, lactoferrin, C3bc and TCC were lower in the heparin-coated group compared to the control group. The increases in plasma myeloperoxidase and lactoferrin correlated significantly to the increase in CD11b (r = 0.71, p = 0.02 and r = 0.64, p = 0.05, respectively) and CD11c (r = 0.72, p = 0.008 and r = 0.72, p = 0.008, respectively) on granulocytes, suggesting interacting regulatory pathways in the process of neutrophil adhesion, activation and degranulation. Thus, in this in vitro ECC model, heparin coating of oxygenator/tubing sets reduced leucocyte activation and leucocyte adhesion-related phenomena.

Blood Cell Count

A new method for isolation of smooth muscle cells from human umbilical cord arteries.

A simple method is described for obtaining a large number of single smooth muscle cells by enzymatic digestion of heparin-perfused human umbilical cord arteries. The smooth muscle cell cultures exhibited the characteristic "hill and valley" growth pattern as seen by phase contrast and scanning electron microscopy. By using indirect immunofluorescence or alkaline phosphatase-anti-alkaline phosphatase techniques the cells were identified as smooth muscle cells by the presence of alpha smooth muscle actin and vimentin. The cultures were not contaminated by endothelial cells as demonstrated by the lack of von Willebrand factor immunoreactivity. This method makes it possible to study smooth muscle cells in primary cultures.

Cell Separation

Large intravenous loads of bilirubin photoconversion products, in contrast to bilirubin, do not cause cholestasis in bile acid-depleted pigs.

BACKGROUND: Large intravenous bilirubin infusions in bile acid-depleted pigs (BADP) destroy hepatocyte canalicular membrane microvilli (CMV) and cause cholestasis. This study examines whether bilirubin photoconversion product infusions do the same. METHODS: The effects of systemic infusion of 135 mumol.kg-1 body weight bilirubin photoconversion products on CMV density and choleretic response to intraportal bile acid infusion were studied in BADP. Furthermore, the effects of 135 mumol.kg-1 b.w. bilirubin infusion, either through an arteriovenous bilirubin photoconversion shunt device (PCD) or intravenously, were measured in PCD-connected BADP. RESULTS: Intravenous bilirubin photoconversion product infusions affected neither the CMV density nor the choleretic response to cholic acid infusion, and neither did bilirubin infusion through the PCD. In contrast, intravenous bilirubin infusion caused canalicular injury and cholestasis in four of six PCD-connected BADP. CONCLUSION: Bilirubin photoconversion products do not destroy CMV or cause cholestasis in BADP. A bilirubin photoconversion shunt device can confer cholestasis protection to bilirubin-loaded BADP.

Animals

Soft tissue response to polytetrafluoroethylene and silicone rubber in humans: morphological and immunohistochemical observations.

The objective of this study was by morphological and immunohistochemical means to investigate the cellular tissue response to the alloplastic materials polytetrafluoroethylene (PTFE polymer), and soft and hard silicone rubber over time. In seven healthy volunteers implants made of Proplast-Teflon, and soft and hard silicone were inserted subcutaneously in unloaded areas in the iliac crest region. After 1, 2, 4, 12, and 26 weeks, respectively, the implants with surrounding soft tissue were removed en bloc for histological and immunohistochemical examination using a panel of antibodies to various leukocyte markers. The tissue reaction to the various alloplastic materials varied greatly with the focus on macrophage and giant cell reactions and eventual formation of a peri-implant fibrous capsule. The most extensive changes developed next to porous Proplast, both with respect to degree of changes and endurance of tissue reaction. Less intense reactions were seen, in decreasing order, to soft silicone, Teflon, and hard silicone. The study gave no clues to a toxic, allergic, or traditional immunological pathogenesis of the tissue reaction induced by the test materials.

Adult

[Reconstruction of the jaw and oral cavity with free vascularized grafts].

59 microvascular graft transfers performed in 50 patients in our department since 1985 have been studied retrospectively. The indications for microvascular reconstruction were sequelae after tumour surgery in 38 patients, gunshot injury in seven, chronic osteomyelitis of the mandible in three, complication after jaw fracture in one patient, and atrophy of the alveolar ridge also in one patient. Transplants from the iliac crest, fibula, radius, radial forearm skin and jejunum were used. Three transplants were lost because of arterial thrombosis, giving a success rate of 94.9%. Complications were registered in 19 cases, the largest group being wound infections. 21 of the 50 patients have been treated with dental implants for total rehabilitation of masticatory function. Transfer of free vascularized bone and soft tissue grafts has greatly improved the functional and cosmetic results obtained in reconstructive surgery of the orofacial region.

Adolescent

[Craniofacial surgery].

Craniofacial surgery is the term given to surgical techniques which allow combined access to the neurocranium and the facial skeleton. These techniques are applied primarily for treatment of fractures of the frontal/nasal/orbital regions, tumours of the orbits and the anterior cranial base, and congenital malformations, including simple or complex craniofacial synostoses, e.g. Crouzon and Apert syndromes. Indications for surgical treatment and the timing of the surgery are discussed. In addition, the most common surgical techniques are described and some clinical cases are presented.

Child, Preschool