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Biomedical subjects

R Andersson

Publications and source records attributed to R Andersson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Roles of platelet-activating factor, interleukin-1beta and interleukin-6 in intestinal barrier dysfunction induced by mesenteric arterial ischemia and reperfusion.

BACKGROUND: Platelet-activating factor (PAF), cytokines, proteases, and other factors are probably involved in the development of gut barrier dysfunction following intestinal ischemia and reperfusion (I/R), although the act underlying pathophysiological mechanisms has not yet been fully clarified. The aim of the present study was to clarify the relationship of intestinal barrier integrity to systemic levels of interleukin-1beta, interleukin-6, and protease inhibitor levels and local leukocyte accumulation in a rat model of intestinal ischemia for 40 min followed by 3 or 12 h reperfusion, with or without treatment with a PAF inhibitor. METHODS: Myeloperoxidase (MPO) content in the small intestinal mucosa, serum levels of interleukin-1beta and -6, and plasma protease inhibitors, and intestinal endothelial and epithelial permeability were assessed, with or without treatment with the PAF antagonist lexipafant. RESULTS: Intestinal I/R resulted in intestinal barrier dysfunction with pronounced plasma leakage to the intestinal lumen, the leakage being aggravated following a longer reperfusion period. Proteolytic plasma activity was evident by low levels of the plasma protease inhibitors measured. MPO content increased significantly after I/R, as did serum levels of interleukin-1beta and -6, without difference between the two periods of reperfusion. Treatment with the PAF inhibitor lexipafant partly, though not fully, restored the changes caused by I/R. CONCLUSION: PAF seems to be involved in the release of cytokines, such as interleukin-1 and -6, consumption of protease inhibitors, and impaired intestinal barrier integrity seen following intestinal I/R. Treatment with a PAF antagonist was effective in restoring the changes caused by intestinal I/R, though not reaching complete normal levels.

Animals↗
PubMed1999

Influence of bile duct stones on patient features and effect of endoscopic sphincterotomy on early outcome of edematous gallstone pancreatitis.

The objective of this study was to study the influence on patients' features and the effect on early outcome of the presence of bile duct stones and endoscopic sphincterotomy (EST), respectively, in the presence of edematous gallstone pancreatitis (GSP). It was a retrospective review of a patient series from 1981 through 1992 at a university teaching hospital. Altogether 96 patients aged 42 to 93 years (median 74 years) with edematous GSP were investigated by endoscopic retrograde cholangiography (ERC) in our department, 75 of whom underwent ERC at first admission. A total of 49 patients (group 1) had common bile duct (CBD) stones, and in 47 (group 2) no CBD stones were found. All patients in group 1 and 15 in group 2 underwent EST; 57 of the 75 patients had EST at first admission. The main outcome measures were pancreas-related complications and the length of the hospital stay. The early major complication and stone clearance rates of the EST procedure were 3.2% and 96%, respectively. Duration of symptoms prior to ERC was similar in groups 1 and 2 (median 5 and 8 days, respectively). Serum amylase activity was higher in group 2 patients than in group 1 patients [21-258 (median 75) microkat/L vs. 10-328 (median 48) microkat/L (p = 0.01)], but the length of hospital stay was similar: [4-39 (median 11) days vs. 4-19 (median 9) days (p = 0.05)]. Cholangitis at acute admission was more common in group 1 than in group 2 patients (31% vs. 7%; p = 0. 02), whereas a history of pancreatitis was noted more often in group 2 patients (49% vs. 8%; p< 0.001). ERC was done 1 to 18 days (median 2 days) and 1-16 days (median 5 days) (p = 0.02) after admission in groups 1 and 2 respectively, because of the more frequent cholangitis symptoms in group 1. It was concluded that the history and features at admission differed between patients with and without CBD stones at ERC done during an attack of GSP. Early EST had no influence on outcome or hospitalization. This study does not support routine EST in conjunction with mild GSP.

Adult↗
PubMed1999

Inhibition of platelet-activating factor, intercellular adhesion molecule 1 and platelet endothelial cell adhesion molecule 1 reduces experimental pancreatitis-associated gut endothelial barrier dysfunction.

BACKGROUND: Endothelial barrier dysfunction is a critical link in the development of tissue injury and organ dysfunction, via upregulation and exposure of adhesion molecules, intercellular signals and leucocyte-endothelial cell interactions. Inhibitors of inflammatory mediators and receptors have been suggested as a means of downregulating the cascade of both local and systemic inflammation. METHODS: The potential therapeutic inhibition of platelet-activating factor (PAF), intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 was investigated in pancreatitis-associated gut endothelial dysfunction in rats, by treatment with a PAF antagonist (lexipafant, BB-882) and monoclonal antibodies against rat ICAM-1 (anti-ICAM1-Mb) and PECAM (anti-PECAMA1-Mb). Alterations in gut endothelial barrier dysfunction and leucocyte recruitment, and systemic levels of interleukins were evaluated. RESULTS: Plasma exudation measured by the albumin leakage index and tissue leucocyte recruitment in the distal small intestine and colon increased significantly 12 h after induction of pancreatitis and treatment with saline. These alterations were to varying degrees counteracted by treatment with lexipafant, anti-ICAM1-Mb or anti-PECAM1-Mb. Alterations in levels of interleukin (IL) 1 paralleled the changes in gut endothelial barrier dysfunction and leucocyte trapping. CONCLUSION: Treatment with lexipafant and monoclonal antibodies against ICAM-1 or PECAM-1 reduced the severity of pancreatitis-associated gut endothelial dysfunction, and decreased systemic concentrations of IL-1 and local leucocyte recruitment.

Animals↗
PubMed1999

Diverse T-cell receptor CDR3 length patterns in human CD4+ and CD8+ T lymphocytes from newborns and adults.

T cells are essential in the initiation and maintenance of immune responses. Specific interaction between T cells and a presumptive antigen occurs through recognition of an MHC-peptide complex by the T-cell receptor (TCR). The complementarity-determining region (CDR) 3 of the TCR has direct contact with the peptide. Here we describe CDR3 length variability of six different TCRBV gene families of CD4+ and CD8+ umbilical cord (UC) and peripheral blood (PB) T cells. Amplified products spanning the TCR CDR3 regions from CD4+ PB, CD4+ UC and CD8+ UC blood T cells typically displayed Gaussian-like distributions. In contrast, profound and frequent perturbations were recorded in CD8+ PB lymphocytes, with a non-Gaussian pattern in more than half of the samples studied. A substantial portion of the perturbed CD8+ subsets were clonal or oligoclonal, as determined by CDR3-length restriction, TCRBJ gene usage and nucleotide sequencing. This implies that the conditions for shaping and maintenance of the peripheral TCR repertoire are profoundly different for CD8+ and CD4+ T cells.

Adult↗
PubMed1999

Potential mechanisms responsible for zymosan-associated endothelial injury in rats.

OBJECTIVE: To assess alterations in endothelial barrier integrity and potential factors involved in zymosan-associated endothelial injury. DESIGN: Experimental study. SETTING: University hospital, Sweden. ANIMALS: 42 adult male Sprague-Dawley rats. INTERVENTIONS: One hour before an intraperitoneal injection of paraffin or zymosan (0.25 mg/g body weight), 1.0 ml of a solution of saline, N-acetyl-L-cysteine, dimethyl sulphoxide, indomethacin, verapamil, or allopurinol was given intravenously. MAIN OUTCOME MEASURES: Measurement of tissue water content, tissue intravascular plasma volume, interstitial fluid volume, and extravascular 125I-labelled human serum albumin distribution as well as plasma concentrations of albumin, alpha1-macroglobulin, alpha2-antiplasmin, and antithrombin III, 24 hours after the intraperitoneal injection. RESULTS: Endothelial permeability significantly increased in abdominal organs and the gastrointestinal tract, and plasma antiplasmin concentrations decreased. Pretreatment with N-acetyl-L-cysteine, dimethyl sulphoxide, or indomethacin protected against zymosan-induced endothelial barrier injury and the decline in protease inhibitors in plasma to varying degrees, while pretreatment with verapamil or allopurinol had a limited effect. CONCLUSION: Oxygen free radicals, prostaglandin, and proteases may have roles in the pathogenesis of zymosan-induced endothelial barrier injuries, implying that several mediators probably are interacting.

Animals↗
PubMed1999

Unintentional injury mortality in children: a priority for middle income countries in the advanced stage of epidemiological transition.

OBJECTIVES: To examine the relationship between the magnitude, and the relative importance of unintentional child injury mortality with socioeconomic development, and to conceptualise the dynamic changes in injury mortality within the framework of epidemiological transition. DESIGN: Ecological cross sectional study using data on 51 countries. MAIN OUTCOME MEASURES: The relationship between total mortality rates, unintentional injury mortality rates, and percentage in children 1-14 years of age with gross national product (GNP) per capita. RESULTS: Unintentional injury mortality rates in children were negatively correlated with GNP per capita. However, by categorising the data, we found some areas of non-correlation: in children 5-14 years in low income versus lower middle income countries, and in all age and gender groups in lower high income versus higher high income countries. A high percentage of total deaths due to injuries was clearest in the lower middle income countries in all age and gender groups. CONCLUSIONS: The changes in child injury mortality in relation to socioeconomic development could be conceptualised as three stages: a stage of high magnitude; a stage of high priority; and a stage of improvement. Most middle income countries are in the high priority stage where both injury mortality rates and injury percentage of total deaths are high.

Adolescent↗
PubMed1999

Long-term changes in gastrin, cholecystokinin and insulin in response to oxytocin treatment.

The present study was designed to investigate how repeated injections of oxytocin influence plasma levels of vagally controlled hormones such as gastrin, cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous oxytocin and glucose. Since oxytocin may enhance the activity of centrally located alpha2-adrenoreceptors, a second aim of this study was to explore whether these receptors are involved in the effects. For this purpose, oxytocin (1.0 mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was collected and hormone levels were radioimmunoassayed. The oxytocin treatment caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and 10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA; p < 0.01). In addition, both insulin and CCK levels were decreased in response to the oxytocin treatment when measured 3 and 10 days after the last injection (ANOVA; insulin p < 0.01, CCK p < 0.05). When the alpha2-adrenoreceptor agonist clonidine (2.5 microgram/kg intracerebroventricularly) was administered 3 days after the 5-day treatment period with oxytocin or saline, plasma levels of insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats, when compared to saline-treated controls receiving clonidine only. No change in glucose or somatostatin levels was found in response to the oxytocin treatment. In conclusion, these results show that oxytocin induces long-lasting changes in plasma levels of gastrin, CCK and insulin, without affecting somatostatin or glucose levels. These effects may be mediated by changes in vagal nerve activity.

Adrenergic alpha-Agonists↗
PubMed1999

Treatment with lexipafant ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic pancreatitis.

CONCLUSION: Treatment with lexipafant reduced the severity of pancreatitis-associated endothelial barrier compromise, also associated with a decrease in systemic concentrations of interleukin (IL) 1. Thus, the present findings imply that platelet-activating factor (PAF) may play an important role in the pathogenesis of pancreatic endothelial dysfunction by signaling and triggering the production and release of certain cytokines. BACKGROUND: Pancreatic capillary endothelial barrier dysfunction is an initial and characteristic feature of acute pancreatic injury and pancreatitis. PAF, a proinflammatory mediator and an intercellular signaling substance, has been considered to be involved in the inflammatory reaction and the systemic endothelial dysfunction of acute pancreatitis. METHODS: The development of pancreatic capillary endothelial barrier dysfunction was monitored by tissue edema and exudation of plasma albumin into the interstitium, 3 and 12 h after induction of acute pancreatitis by intraductal infusion of 5% sodium taurodeoxycholate in rats. Pancreatic leukocyte recruitment was reflected by measuring myeloperoxidase activity. Serum levels of IL-1 beta and IL-6 were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Pretreatment with lexipafant, a potent PAF receptor antagonist, significantly reduced the pancreatitis-induced increase in pancreatic endothelial barrier dysfunction, pancreatic leukocyte recruitment and serum levels of IL-1 beta, although a difference persisted between animals with sham operation and pancreatitis.

Acute Disease↗
PubMed1999

Gut barrier dysfunction in experimental acute pancreatitis.

Bacterial infections, frequently caused by bacteria of enteric origin, are often seen during the progression of severe acute pancreatitis, concomitant with the potential development of multiple organ dysfunction. In the present paper, the complex mechanisms of gut barrier dysfunction and gut origin sepsis in acute pancreatitis are discussed. The individual parts of the gut barrier, e.g. the immunological, bacteriological and morphological (mucus, epithelium, endothelium and interstitium) components, seem to interact and depend on each other. Pancreatitis-induced hypovolaemia due to endothelial barrier leakage and gut arteriovenous shunting causes intestinal ischaemia and reperfusion injury with concomitant gut barrier dysfunction. Gut endothelial barrier dysfunction probably plays a central role. Potential molecular mechanisms could, among others, be associated with alterations in intracellular signal transduction, intercellular signalling and expression of adhesion molecules on endothelial cells. The mechanisms underlying gut barrier dysfunction in acute pancreatitis are thus complex and still not fully elucidated. Knowledge about the regulating events will probably allow future pharmacological therapy for prevention and treatment of the severe complications of acute pancreatitis, including gut barrier dysfunction.

Acute Disease↗
PubMed1999

The influence of supplements of selenite, selenate and selenium yeast on the selenium status of dairy heifers.

The aim of the study was to define possible differences between selenite, selenate and selenium yeast on various aspects of selenium status in growing cattle. Twenty-four Swedish Red and White dairy heifers were fed no supplementary selenium for 6 months. The basic diet contained 0.026 mg selenium/kg feed dry matter (DM). After the depletion period the animals were divided into 4 groups; group I-III received 2 mg additional selenium daily as sodium selenite, sodium selenate, and a selenium yeast product, respectively. Group IV, the control group, received no additional selenium. The total dietary selenium content for groups I-III during the supplementation period was 0.25 mg/kg DM. After the depletion period the mean concentration of selenium in blood (640 nmol/l) and plasma (299 nmol/l) and the activity of GSH-Px in erythrocytes (610 mukat/l) were marginal, but after 3 months of supplementation they were adequate in all 3 groups. The concentration of selenium in blood and plasma was significantly higher in group III than in groups I and II, but there was no significant difference between groups I and II. The activity of GSH-Px in erythrocytes did not differ between any of the supplemented groups. The animals in the control group had significantly lower concentrations of selenium in blood and plasma and lower activities of GSH-Px in erythrocytes than those in the supplemented groups. The activity of GSH-Px in platelets was also increased by the increased selenium intake. There was no difference in the concentration of triiodothyronine (T3) between any of the groups, but the concentration of thyroxine (T4) was significantly higher in the unsupplemented control group.

Animals↗
PubMed1998

Impaired antibody responses in H-2Ab mice.

In murine in vivo systems, Ags administered in physiologic solutions together with specific IgE induce a significantly higher Ab response than Ags administered alone. In vitro, IgE in complex with Ag enhances B cell-mediated presentation of the Ag to T cells. Both phenomena require an intact low affinity receptor for IgE (Fc epsilon RII/CD23), suggesting that the effect on in vivo Ab responses is caused by increased Ag presentation. We here show that mice carrying the MHC class II Ab molecule (e.g., C57BL/6 and 129/Sv) do not produce Abs to BSA when immunized with BSA-2,4,6-trinitrophenyl (TNP) in complex with monoclonal IgE anti-TNP. In contrast, strains of all other MHC haplotypes tested (H-2d, H-2k, H-2p, H-2q, and H-2s) respond vigorously to IgE/BSA-TNP complexes, with Ab responses several hundred-fold higher than the responses in H-2b mice. C57BL/6 mice were unable to produce a carrier-specific response also after immunization with IgE/OVA-TNP, IgE/diphtheria toxoid-TNP, or IgE/tetanus toxoid-TNP. Although the low responsiveness mapped to the Ab region, responsiveness was not restored in C57BL/6 mice carrying transgenic Ak, suggesting that a nonclassical A-region-encoded gene product is involved. Most importantly, our data call attention to the fact that the C57BL/6 and 129 mouse strains, which are widely used for producing transgenic animals, have defective immune responses.

Animals↗
PubMed1998

Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc of immunoglobulin G suppresses experimental autoimmune encephalomyelitis.

We explore here if vaccination with DNA encoding an autoantigenic peptide can suppress autoimmune disease. For this purpose we used experimental autoimmune encephalomyelitis (EAE), which is an autoaggressive disease in the central nervous system and an animal model for multiple sclerosis. Lewis rats were vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig myelin basic protein peptide 68-85 (MBP68-85), before induction of EAE with MBP68-85 in complete Freund's adjuvant. Compared to vaccination with a control DNA construct, the vaccination suppressed clinical and histopathological signs of EAE, and reduced the interferon gamma production after challenge with MBP68-85. Targeting of the gene product to Fc of IgG was essential for this effect. There were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding autoantigenic peptides may be useful tools in controlling autoimmune disease.

Animals↗
PubMed1998

Molecular and genetic requirements for preferential recruitment of TCRBV8S2+ T cells in Lewis rat experimental autoimmune encephalomyelitis.

The underlying mechanisms behind the preferential expression of select TCRBV products in certain autoimmune illnesses, such as multiple sclerosis and some models of experimental autoimmune encephalomyelitis (EAE), have principally remained enigmatic. In this study, we examined the mutual role of nonself- vs self-origin of antigenic myelin basic protein (MBP) peptides and given MHC haplotypes in relation to the relative frequency of activated TCRBV8S2+ T lymphocytes in the Lewis (LEW) rat EAE model. Inbred MHC (RT1) congenic LEW rats (LEW (RT1l), LEW.1AV1 (RT1av1), and LEW.1W (RT1u)) were immunized with the 63 to 88 peptide of the guinea pig MBP (MBPGP63-88). Additionally, LEW rats were immunized with the corresponding autologous rat sequence (MBPRAT63-88). Although EAE ensued in all MBP peptide/LEW rat strain combinations, only LEW rats immunized with the heterologous MBPGP63-88 peptide elicited T cell responses encompassing a bias toward TCRBV8S2 expression, as determined by flow cytometric analyses. Reduction of TCRBV8S2+ T cells led to mitigation of disease severity in LEW rats immunized with MBPGP63-88, but not with MBPRAT63-88, indicating that critical encephalitogenic characteristics are associated with this T cell subset. We conclude that the preferential recruitment of TCRBV8S2+ T cells in the LEW rat EAE model is due to selective, high-avidity recognition of the nonself-MBPGP63-88 in the context of the RT1.Bl molecule. This inference lends support to the notion that the highly restricted TCR repertoire of the self-MBP-reactive T cells in certain genetically predisposed multiple sclerosis patients may have its source in a multistep molecular mimicry event.

Amino Acid Sequence↗
PubMed1998

Liver resection of noncolorectal secondaries.

BACKGROUND AND OBJECTIVES: Hepatic resection of noncolorectal metastases appears to be performed with increasing frequency. Reported experience is limited and indications are controversial. METHODS: Retrospective review of curative hepatic resection in 32 patients (median age 58 years) during 1970-1995. The primary tumor was a carcinoid in seven patients, other endocrine tumor in five patients, malignant melanoma in three patients, stomach cancer in three patients, exocrine pancreatic cancer in two patients, gynecological cancer in two patients, sarcoma in two patients, and miscellaneous in eight patients. Seven patients (22%) had bilobar disease and 12 patients (38%) had extrahepatic growth. RESULTS: Median survival was 32 months, and 5-year actuarial survival rate was 36% (including operative mortality). Median survival in the endocrine (n = 12) and nonendocrine (n = 20) groups was 72 and 18 months, respectively (corresponding 5-year survival rates were 56 and 25%) (P = 0.16). Prognostic factors could not be established in either group. It is, however, noteworthy that no patient with nonendocrine secondaries and more than one liver tumor or extrahepatic disease survived for 5 years. Major complications were seen in eight patients (25%), including three postoperative deaths (operative mortality 9%) occurring during the first 5 years of the study period. CONCLUSIONS: Hepatic resection of metastases from endocrine primary tumors was followed by long-term survival in a substantial proportion of patients. Long-term survival for patients with nonendocrine tumors was observed only when there was a single liver tumor and no extrahepatic growth. Further experience is needed for definition of resection criteria.

Actuarial Analysis↗
PubMed1998

[Combination therapy in oncology (multimodal treatment) in pancreatic tumors].

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Adenocarcinoma↗