PubMed Health⌕ Search

Biomedical subjects

A Pettersson

Publications and source records attributed to A Pettersson.

At least 19 recordsLinked to original sources
PubMed2004

Polybrominated diphenylethers and methoxylated tetrabromodiphenylethers in cetaceans from the Mediterranean Sea.

Eight tetrabrominated to hexabrominated diphenylethers were present at ppb levels in liver from cetaceans found stranded on the beaches of the Mediterranean Sea, Italy. The highest concentration was found in striped dolphin (sum polybrominated diphenyl ethers [PBDE] 8133 ng/g l.w.) and the lowest concentration in bottlenose dolphin (sum PBDE 66 ng/g lipid weight [l.w.]). The predominant congener in all samples was 2,2',4,4'-tetraBDE (PBDE # 47) followed by, in decreasing order, the pentaPBDE # 99 and 100 and the hexaPBDE # 154 and 153. In 12 of the 14 analyzed samples, 3 different methoxylated PBDEs (MeO-PBDE # 1, 2, and 3) were detected at semiquantitatively calculated concentration ranges of 2 to 14 ng/g l.w.; 5 to 167 ng/g l.w.; and 7 to 628 ng/g l.w., respectively. In addition, several unidentified bromine compounds were seen when screening the samples in negative-chemical ionization (NCI) mode monitoring m/z 79 and 81, which illustrates the importance of running both electron-impact ionization and NCI when analyzing environmental samples. Electron-impact ionization is more specific for monitoring the molecular ion compared with NCI, which might overestimate the concentration of certain PBDE congeners.

Animals↗
PubMed2004

CD8alpha dendritic cells and immune protection from experimental allergic encephalomyelitis.

Dendritic cells (DC) represent a phenotypically heterogeneous population endowed with two important biological functions, immunity and tolerance. Here we report that the injection of splenic CD8alpha(+) DC, derived from rats with experimental allergic encephalomyelitis (EAE), delayed the onset and suppressed the severity of EAE in Lewis rats. This was accompanied by the lack of magnetic resonance imaging (MRI) lesions in the brain and spinal cord and by reduced numbers of inflammatory cells within the central nervous system. Injection of CD8(alpha+) DC inhibited T cell proliferation that may relate to increased interferon (IFN)-gamma and nitric oxide production. Although CD8(+)CD28(-) suppressor T cells, apoptotic cells and co-stimulatory molecules were not altered, CD4(+) T cells expressing interleukin (IL)-10 were augmented in rats receiving CD8alpha(+) DC compared to rats receiving total DC or medium. These results demonstrate that rat splenic CD8alpha(+) DC could provide a cellular basis for a novel, individualized immunotherapy using autologous DC as a complement to conventional therapy in diseases with an autoimmune background such as multiple sclerosis.

Animals↗
PubMed2004

The - 564 A/G polymorphism in the promoter region of the proteinase 3 gene associated with Wegener's granulomatosis does not increase the promoter activity.

Proteinase 3 is the major autoantigen in patients with Wegener's granulomatosis. Earlier studies have shown that circulating leucocytes from patients with Wegener's granulomatosis show elevated proteinase 3 surface expression and mRNA levels. Wegener's granulomatosis patients also have increased levels of proteinase 3 in plasma. A single nucleotide polymorphism (SNP) (-564 A/G SNP) in the promoter region has been associated with disease. This SNP introduces a new potential Sp1 transcription factor binding site that may be responsible for the observed up-regulated expression of proteinase 3. To investigate this a 740 base pair long region of the promoter was cloned from genomic DNA. The disease-associated -564 A/G, as well as a control -621 A/G exchange, were introduced by polymerase chain reaction mutagenesis and cloned into a luciferase reporter vector. Endogenous expression levels of proteinase 3 mRNA and promoter activity of the cloned constructs were measured in three myeloid cell lines, HL-60, U937 and NB-4, and in epithelial HeLa cells. The results demonstrate a good correlation between the endogenous proteinase 3 mRNA expression and the promoter activity, as judged by luciferase activity. However, no significant differences in activity between the wild-type, polymorphic and the mutated control variant were found. In conclusion, the -564 A/G polymorphism is not responsible for the increased expression levels seen in myeloid cells from patients with Wegener's granulomatosis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

Interleukin-10-modulated immature dendritic cells control the proinflammatory environment in multiple sclerosis.

Multiple sclerosis (MS) is a disabling, inflammatory, demyelinating disease of the central nervous system considered to be mediated by autoreactive T cells. Dendritic cells (DC), being professional antigen-presenting cells, play a pivotal role in the decision between T-cell activation and anergy. It has been suggested that mature DC (mDC) induce immunity, whereas immature DC (imDC) have the potential to induce tolerance. In this study, we investigated the effects of autologous imDC versus autologous mDC on lymphocytes with respect to the expression of functionally important cell-surface molecules and production of cytokines. Our aims were to investigate whether the maturation status of DC differs between MS and healthy controls (HC) and to explore whether the effects of DC on T-cell responses differ between MS and HC. DC were generated from adherent blood mononuclear cells from patients with MS and HC. imDC were obtained by culture with either granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) or GM-CSF + IL-4 + IL-10. mDC were obtained by adding lipopolysaccharide to DC cultures. Upon coculture with autologous lymphocytes, mDC activated the autologous T cells as reflected by increased CD25 and cytotoxic T-lymphocyte antigen-4 expression on CD4(+) T cells together with the increased production of both T helper 1 (Th1) (IL-2 and interferon-gamma) and Th2 (IL-10 and IL-4) cytokines. Unmodulated naïve imDC induced the production of only IL-4. An exposure of imDC to IL-10 induced the production of IL-4 as well as IL-10 by autologous lymphocytes. We hypothesize that such imDC are important in controlling the proinflammatory environment in vivo in patients with MS.

Adult↗
PubMed2003

Effects of dietary nitrate on oesophageal motor function and gastro-oesophageal acid exposure in healthy volunteers and reflux patients.

BACKGROUND/AIMS: High concentrations of nitric oxide (NO), derived from dietary nitrite in an acid environment, have been demonstrated in the gastric fundus and in the oesophagus. The aim of this study was to investigate whether luminal NO can influence oesophageal smooth muscle performance, lower oesophageal sphincter (LOS) function or gastric and oesophageal acid exposure. METHODS: Eleven healthy volunteers and 9 patients with chronic gastro-oesophageal reflux disease (GORD) received a diet deprived of nitrate/nitrite but supplemented with placebo or potassium nitrate for 4 days in a randomised order. On day 4 in each trial period, manometry was performed including a sleeve sensor registration of the LOS followed by a simultaneous 24-hour intra-gastric and oesophageal pH registration. RESULTS: Nitrate supplementation increased the proportion of effective peristalsis when analysed for the entire study population. No other significant effects of dietary nitrate were found on oesophageal motor variables, on the sphincter resting tone or on the number or duration of transient sphincter relaxations. No effect was found on either gastric acidity or gastro-oesophageal reflux variables. Major reflux symptoms were not influenced by nitrate administration. CONCLUSION: Dietary nitrate did not significantly affect oesophageal motor or LOS function, gastro-oesophageal acid reflux or reflux symptomatology either in healthy volunteers or in GORD patients.

Adult↗
PubMed2003

Differential inhibition of receptor activation by two mouse monoclonal antibodies specific for the human leukotriene B4 receptor, BLT1.

The inflammatory mediator leukotriene B(4) (LTB(4)) binds to and activates a G-protein-coupled receptor named BLT(1). We have previously produced two monoclonal antibodies, named 7B1 and 14F11, that bind specifically to this receptor. Using a HeLa cell line expressing human BLT(1), we find that both antibodies inhibit LTB(4)-induced calcium release, and activation of a MAP-kinase-sensitive luciferase reporter system. The normal chemotactic movement of polymorphonuclear cells towards higher LTB(4) concentrations was also strongly inhibited by both antibodies. Neither antibody was found to activate BLT(1), and experiments using cyclic peptide fragments of the BLT(1) n-terminal and extracellular loops showed that these antibodies bind only to complex epitopes in the tertiary, membrane bound, conformation of the receptor protein. In ligand binding experiments, 7B1 was found to be a competitive antagonist, while 14F11 was a noncompetitive antagonist that inhibited receptor activation, but not agonist (LTB(4)) binding. 14F11 will be a useful tool for studying the mechanisms of receptor activation.

Animals↗
PubMed2003

Oesophageal intraluminal nitric oxide facilitates the acid-induced oesophago-salivary reflex.

BACKGROUND: The present study explores some aspects of the triggering of the acid-induced oesophago-salivary reflex. In addition to hydrogen ions, there are two acid-dependent molecules with messenger potential in the oesophageal lumen: CO2 and NO. The aim of this study was to clarify whether oesophageal NO and CO2 participate in the regulation of salivary neutralizing capacity in response to acid exposure. METHODS: Healthy volunteers received oesophageal acidification composed of HCl, with NO3-, or HCO3- or NO3- and HCO3- in combination. In a second series of experiments, the exposure period was divided into 2 separate 10-min events. Saliva volume and titratable buffering capacity were used to calculate alkaline secretion. RESULTS: Salivary alkaline secretion increased markedly following 20 min intraluminal exposure to HCl. The initial part of this response was 22% +/- 2.2% larger (P < 0.05) if NO3- was present. When HCO3- was added, or if NO3- and HCO3- were given simultaneously, the secretory response tended to be lower. The accumulated responses over 70 min to 2 short HCl exposures (10 min each separated by a 30 min 'rest') compared to one long one lasting 20 min were similar regardless of the presence of NO3-. CONCLUSION: The data suggest that oesophageal intraluminal NO facilitates initiation of the oesophago-salivary reflex. CO2 seems to have a negligible effect on alkaline salivation, and repeated stimulation does not influence the magnitude of the response over time.

Adult↗
PubMed2003

Stimulated murine macrophages as a bioassay for H. pylori-related inhibition of nitric oxide production.

BACKGROUND: Interference with the L-arginine/nitric oxide pathway may be a virulence strategy for the gastric pathogen Helicobacter pylori. This study evaluates a bioassay for such inhibitory actions on nitric oxide synthase. METHODS: Cultured murine macrophages were stimulated by lipopolysaccharide and interferon-gamma. Nitric oxide synthesis and the expression of inducible nitric oxide synthase (iNOS) at increasing concentrations of L-arginine were analysed using chemiluminescence and Western blotting, respectively. RESULTS: The bioassay was evaluated against nitrite accumulation and two established NOS inhibitors. Bacterial extracts or whole cells of one H. pylori strain inhibited nitric oxide production at low L-arginine concentrations (2-20 microM). A higher concentration of L-arginine (200 microM) was not associated with such inhibition. The iNOS expression was not affected by any of the additives compared to stimulated controls. CONCLUSIONS: This bioassay is a reliable and simple method for analysing iNOS inhibition, resolving effects on enzyme activity or enzyme expression. H. pylori water extract and whole cells exert an L-arginine-dependent NOS inhibition, not influencing iNOS expression.

Animals↗
PubMed2003

Prevalence of dental resorptive lesions in Swedish cats.

Ninety-six, randomly selected Swedish cats were evaluated for the presence of dental resorptive lesions. All cats were examined while receiving general anesthesia. Diagnosis was based on oral examination and full-mouth, intraoral dental radiographs. Information concerning age, sex, vaccination status, eating habits, food type, environment (indoor or outdoor housing), oral, discomfort, dental care, and medical treatment was recorded. Hematologic samples included analysis for FeLV, FIV, and calcivirus. Of the cats examined in this study, 32% had gross or radiographic signs of dental resorptive lesions. There was a positive relationship between the occurrence of dental resorptive lesions and increasing age.

Animals↗
PubMed2002

A listeriosis patient infected with two different Listeria monocytogenes strains.

Normally, only one isolate of Listeria monocytogenes from a case of listeriosis is subjected to characterization. Here we show that two isolates from different sites of the body were not the same strain. Such a phenomenon may not have any clinical relevance, although it may confuse the epidemiologist trying to match infection source with infection target.

DNA, Bacterial↗
PubMed2002

Sources of intra-oesophageal nitric oxide production following intraluminal acid exposure.

BACKGROUND: The aim of the present study was to assess luminal nitric oxide (NO) levels in the oesophagus during baseline and acidic conditions and to clarify the sources of such oesophageal NO formation. METHODS: Healthy volunteers received an intra-oesophageal infusion of either HCl (100 mM) or NaCl (50 mM) on two separate study days. After a low nitrate diet, nitrate load or no dietary restrictions/pretreatment, direct intraluminal measurements of NO formation were performed using a tonometric technique. Endoscopy was performed and mucosal biopsies were taken and analysed by means of immunohistochemistry, Western blot and RT-PCR. RESULTS: No intra-oesophageal NO was detected during baseline conditions with pH neutrality. During the infusion of HCI the NO levels rose dramatically to around 12000 ppb. This high rate of NO formation fell by 95% following deviation of saliva. NO formation after an acute nitrate load was almost doubled during acid perfusion compared to control. Immunohistochemistry demonstrated distinct staining for iNOS in the oesophageal squamous epithelial cells, and Western blot and RT-PCR confirmed the presence of iNOS. CONCLUSION: Two sources exist for intra-oesophageal NO formation, both dependent on the luminal acidity: 1) chemical reduction of salivary nitrite, a mechanism related to dietary intake of nitrate, and 2) NO formation within the oesophageal mucosal epithelium by enzymatic degradation of L-arginine. In the latter case, the NO synthase has antigenic characteristics, indicating the inducible isoform, although a functional behaviour suggests an unconventional subtype.

Adolescent↗
PubMed2002

Helicobacter pylori infection inhibits antral mucosal nitric oxide production in humans.

BACKGROUND: Inducible NO synthase expression is upregulated in H. pylori-infected gastric mucosa, suggesting increased NO synthesis as part of a host defense reaction. This study investigates actual NO production in the human antrum in situ. METHODS: Gastroscopy with antral biopsy sampling and intragastric tonometric NO assessments were performed on H. pylori-positive and -negative volunteers. The antral mucosal specimens were analyzed with regard to inducible NO synthase (Western blotting) and the presence of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) as well as L-arginine. RESULTS: Mucosal expression of inducible NO synthase was markedly increased in H. pylori infected subjects compared to noninfected ones. The ratio between the tissue contents of L-arginine and asymmetric dimethylarginine was considerably lower in the infected group. Antral output of NO was similar in the two groups during baseline conditions. Following intragastric L-arginine exposure. the antral NO production in controls was unaltered (from 442 ppb +/- 104 to 286 ppb +/- 94), whereas it increased (from 524 ppb +/- 162 to 1066 ppb +/- 274) in the infected individuals. CONCLUSIONS: The study confirms that NO synthase expression is increased in H. pylori-infected antral mucosa. However, NO synthesis is restricted owing to the presence of pathogen-induced competitive NO synthase inhibitors such as methylated arginines.

Adolescent↗
PubMed2001

Jejunal luminal nitric oxide during severe hypovolemia and sepsis in anesthetized pigs.

OBJECTIVE: Lowered gut blood perfusion and the associated intestinal mucosal barrier dysfunction is considered important in the pathophysiology leading to critical illness. Intestinal mucosal nitric oxide formation has been attributed a key role in the regulation of epithelial permeability and other properties of the intestinal mucosal barrier. This study was performed to delineate intestinal mucosal NO formation during hypovolemia or sepsis, both of which are associated with intestinal hypoperfusion. MATERIALS AND METHODS: Seventeen pigs were subjected to 2 h of severe hypovolemia (bleeding induced) or sepsis (systemic infusion of live Escherichia coli) or no treatment (controls). Jejunal mucosal NO production was monitored by a tonometer. Mesenteric blood flow was measured as portal venous blood flow by an ultrasonic transit time flowmeter probe, and oxygen delivery and consumption were calculated from regional blood samples. RESULTS: Intestinal perfusion and oxygen delivery were reduced by the same order of magnitude in both groups. Jejunal mucosal NO production and oxygen consumption decreased markedly in the hypovolemia group but remained stable in the group subjected to septic shock. CONCLUSIONS: These data suggest that blood loss inhibits jejunal mucosal NO production as part of a general downregulation of nonvital organs. Sepsis represents a more complex stress condition with activation/maintenance of host defense mechanisms as reflected by maintained jejunal mucosal NO production despite reduced gut blood perfusion.

Analysis of Variance↗
PubMed2001

Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects.

BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO2- in relation to endogenous acid production and infection with Helicobacter pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas both pH and NO2- concentration were similar in the two groups. During inhibition of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2- concentration in gastric aspirates were significantly higher in H. pylori positives than in the controls. Furthermore, during omeprazole treatment the intragastric NO levels were almost absent in H. pylori positives, whereas approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton-pump inhibition in H. pylori-infected individuals abolishes the intragastric chemical reduction of swallowed NO2- in the fasting stomach.

Adult↗
PubMed2001

Angiotensin II type 2 receptor-mediated duodenal mucosal alkaline secretion in the rat.

The aims of this study were to elucidate the distribution of angiotensin receptors (AT(1) and AT(2)) in the duodenal wall and to investigate whether AT(2) receptors are involved in the regulation of duodenal mucosal alkaline secretion, which is of importance for the mucosal defense against gastric acid. Immunohistochemistry was used to locate AT(1) and AT(2) receptors in chloralose-anesthetized rats. Duodenal mucosal alkaline output was measured by use of in situ pH-stat titration. Immunohistochemistry demonstrated a distinct staining for both AT(1) and AT(2) receptors in the lamina propria of the villi and also for AT(1) receptors in the muscularis interna. When angiotensin II was infused in the presence of the AT(1) receptor antagonist losartan, mucosal alkaline secretion increased by ~50%. This response was inhibited by the AT(2) receptor antagonist PD-123319. The AT(2) receptor agonist CGP-42112A increased mucosal alkaline secretion by ~50%. This increase was absent in the presence of PD-123319 but not in the presence of losartan or the local anesthetic lidocaine. We conclude that angiotensin II stimulates duodenal mucosal alkaline secretion by activation of AT(2) receptors located in the duodenal mucosa/submucosa.

Anesthetics, Local↗
PubMed2001

Levels of dimethylarginines and cytokines in mild and severe preeclampsia.

BACKGROUND: The objectives were 1. to evaluate if the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine was altered in mild and severe forms of preeclampsia, and 2. to assess the relationship between dimethylarginines and the cytokine response in preeclampsia. METHODS: Asymmetric and symmetric dimethylarginine were measured with high performance liquid chromatography in women with mild (n=13) and severe (n=32) preeclampsia and in normotensive pregnant controls (n=20). Interleukin-4, -6, -8, -10 and tumor necrosis factor-alpha were analyzed by immunoassays in women with mild (n=8) and severe (n=17) preeclampsia and in normotensive pregnant controls (n=14). The Mann Whitney U-test and Spearman Rank test were used for statistical analysis. RESULTS: The plasma levels of dimethylarginine were increased in preeclamptic subjects. The elevation of symmetric dimethylarginine was more pronounced than that of asymmetric dimethylarginine. The control levels of interleukin-6, -8 and -10 were significantly higher at term than at gestational week 32-36. Interleukin-6 and -8 were significantly elevated in subjects with severe, but not mild, preeclampsia, whereas TNF-alpha and IL-10 were not significantly altered. Symmetric dimethylarginine levels correlated significantly with arterial blood pressure and serum levels of creatinine and uric acid. Dimethylarginine levels in plasma were, however, not related to the cytokine response. CONCLUSIONS: Plasma concentrations of both asymmetric and symmetric dimethylarginine were significantly elevated both in mild and severe preeclampsia. Symmetric, but not asymmetric, dimethylarginine correlated to the severity of the condition. Plasma levels of interleukin-6 and -8 were also elevated in severe preeclampsia but no direct correlations were found between these cytokines and dimethylarginines.

Arginine↗
PubMed2001

Enhanced microdialysis of neuropeptides.

An enhanced microdialysis method for neuropeptides is described and some preliminary results of this novel approach are presented. The enhancement is achieved by adding a vehicle (solid support) to the perfusion fluid in order to increase the diffusion coefficient across the membrane and efficiently transport the analytes towards the detector. The microdialysis samples are desalted and then analyzed on an electrospray ionization orthogonal time-of-flight mass spectrometer. The preliminary results show major increase in signal when comparing this new approach of microdialysis with ordinary microdialysis.

Diffusion↗